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Summary Marburg virus (MARV) is among the most virulent pathogens of primates, including humans. Contributors to severe MARV disease include immune response suppression and inflammatory gene dysregulation ("cytokine storm"), leading to systemic damage and often death. Conversely, MARV causes little to no clinical disease in its reservoir host, the Egyptian rousette bat (ERB). Previous genomic and in vitro data suggest that a tolerant ERB immune response may underlie MARV avirulence, but no significant examination of this response in vivo yet exists. Here, using colony-bred ERBs inoculated with a bat isolate of MARV, we use species-specific antibodies and an immune gene probe array (NanoString) to temporally characterize the transcriptional host response at sites of MARV replication relevant to primate pathogenesis and immunity, including CD14+ monocytes/macrophages, critical immune response mediators, primary MARV targets, and skin at the inoculation site, where highest viral loads and initial engagement of antiviral defenses are expected. Our analysis shows that ERBs upregulate canonical antiviral genes typical of mammalian systems, such as ISG15, IFIT1, and OAS3, yet demonstrate a remarkable lack of significant induction of proinflammatory genes classically implicated in primate filoviral pathogenesis, including CCL8, FAS, and IL6. Together, these findings offer the first in vivo functional evidence for disease tolerance as an immunological mechanism by which the bat reservoir asymptomatically hosts MARV. More broadly, these data highlight factors determining disparate outcomes between reservoir and spillover hosts and defensive strategies likely utilized by bat hosts of other emerging pathogens, knowledge that may guide development of effective antiviral therapies.
Jonathan C. Guito; Joseph B. Prescott; Catherine E. Arnold; Brian R. Amman; Amy J. Schuh; Jessica R. Spengler; Tara K. Sealy; Jessica R. Harmon; JoAnn D. Coleman-McCray; Kirsten A. Kulcsar; Elyse R. Nagle; Raina Kumar; Gustavo F. Palacios; Mariano Sanchez-Lockhart; Jonathan S. Towner. Asymptomatic Infection of Marburg Virus Reservoir Bats Is Explained by a Strategy of Immunoprotective Disease Tolerance. Current Biology 2020, 31, 257 -270.e5.
AMA StyleJonathan C. Guito, Joseph B. Prescott, Catherine E. Arnold, Brian R. Amman, Amy J. Schuh, Jessica R. Spengler, Tara K. Sealy, Jessica R. Harmon, JoAnn D. Coleman-McCray, Kirsten A. Kulcsar, Elyse R. Nagle, Raina Kumar, Gustavo F. Palacios, Mariano Sanchez-Lockhart, Jonathan S. Towner. Asymptomatic Infection of Marburg Virus Reservoir Bats Is Explained by a Strategy of Immunoprotective Disease Tolerance. Current Biology. 2020; 31 (2):257-270.e5.
Chicago/Turabian StyleJonathan C. Guito; Joseph B. Prescott; Catherine E. Arnold; Brian R. Amman; Amy J. Schuh; Jessica R. Spengler; Tara K. Sealy; Jessica R. Harmon; JoAnn D. Coleman-McCray; Kirsten A. Kulcsar; Elyse R. Nagle; Raina Kumar; Gustavo F. Palacios; Mariano Sanchez-Lockhart; Jonathan S. Towner. 2020. "Asymptomatic Infection of Marburg Virus Reservoir Bats Is Explained by a Strategy of Immunoprotective Disease Tolerance." Current Biology 31, no. 2: 257-270.e5.
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging human pathogen, endemic in areas of China, Japan, and the Korea (KOR). It is primarily transmitted through infected ticks and can cause a severe hemorrhagic fever disease with case fatality rates as high as 30%. Despite its high virulence and increasing prevalence, molecular and functional studies in situ are scarce due to the limited availability of high-titer SFTSV exposure stocks. During the course of field virologic surveillance in 2017, we detected SFTSV in ticks and in a symptomatic soldier in a KOR Army training area. SFTSV was isolated from the ticks producing a high-titer viral exposure stock. Through the use of advanced genomic tools, we present here a complete, in-depth characterization of this viral stock, including a comparison with both the virus in its arthropod source and in the human case, and an in vivo study of its pathogenicity. Thanks to this detailed characterization, this SFTSV viral exposure stock constitutes a quality biological tool for the study of this viral agent and for the development of medical countermeasures, fulfilling the requirements of the main regulatory agencies.
Unai Perez-Sautu; Se Gu; Katie Caviness; Dong Song; Yu-Jin Kim; Nicholas Paola; Daesang Lee; Terry Klein; Joseph Chitty; Elyse Nagle; Heung-Chul Kim; Sung-Tae Chong; Brett Beitzel; Daniel Reyes; Courtney Finch; Russ Byrum; Kurt Cooper; Janie Liang; Jens Kuhn; Xiankun Zeng; Kathleen Kuehl; Kayla Coffin; Jun Liu; Hong Oh; Woong Seog; Byung-Sub Choi; Mariano Sanchez-Lockhart; Gustavo Palacios; Seong Jeong. A Model for the Production of Regulatory Grade Viral Hemorrhagic Fever Exposure Stocks: From Field Surveillance to Advanced Characterization of SFTSV. Viruses 2020, 12, 958 .
AMA StyleUnai Perez-Sautu, Se Gu, Katie Caviness, Dong Song, Yu-Jin Kim, Nicholas Paola, Daesang Lee, Terry Klein, Joseph Chitty, Elyse Nagle, Heung-Chul Kim, Sung-Tae Chong, Brett Beitzel, Daniel Reyes, Courtney Finch, Russ Byrum, Kurt Cooper, Janie Liang, Jens Kuhn, Xiankun Zeng, Kathleen Kuehl, Kayla Coffin, Jun Liu, Hong Oh, Woong Seog, Byung-Sub Choi, Mariano Sanchez-Lockhart, Gustavo Palacios, Seong Jeong. A Model for the Production of Regulatory Grade Viral Hemorrhagic Fever Exposure Stocks: From Field Surveillance to Advanced Characterization of SFTSV. Viruses. 2020; 12 (9):958.
Chicago/Turabian StyleUnai Perez-Sautu; Se Gu; Katie Caviness; Dong Song; Yu-Jin Kim; Nicholas Paola; Daesang Lee; Terry Klein; Joseph Chitty; Elyse Nagle; Heung-Chul Kim; Sung-Tae Chong; Brett Beitzel; Daniel Reyes; Courtney Finch; Russ Byrum; Kurt Cooper; Janie Liang; Jens Kuhn; Xiankun Zeng; Kathleen Kuehl; Kayla Coffin; Jun Liu; Hong Oh; Woong Seog; Byung-Sub Choi; Mariano Sanchez-Lockhart; Gustavo Palacios; Seong Jeong. 2020. "A Model for the Production of Regulatory Grade Viral Hemorrhagic Fever Exposure Stocks: From Field Surveillance to Advanced Characterization of SFTSV." Viruses 12, no. 9: 958.
Hantaan virus (HTNV) and Puumala virus (PUUV) are pathogenic hantaviruses found in Asia and Europe, respectively. DNA vaccines targeting the envelope glycoproteins of these viruses have been constructed and found to elicit neutralizing antibodies when delivered to humans by various technologies including intramuscular electroporation. Here, we report findings from a Phase 2a clinical trial of a combined HTNV/PUUV DNA vaccine delivered at varying doses and administration schedules using the Ichor Medical Systems TriGrid intramuscular electroporation delivery technology. The study was designed to characterize the effects of DNA vaccine dose and number of administrations on the frequency and magnitude of immunological response. Subjects (n = 120) were divided into four cohorts. Cohorts 1 and 2 received a dose of 2 mg of DNA (1 mg per plasmid), and cohorts 3 and 4 received a dose of 1 mg of DNA (0.5 mg per plasmid) each vaccination. Each of the four cohorts received a series of four administrations (days 0, 28, 56 and 168). For cohorts 1 and 3, the DNA vaccine candidate was delivered at each of the four administrations. For cohorts 2 and 4, in order to maintain blinding, subjects received the DNA vaccine on days 0, 56 and 168, but on day 28 received only the phosphate buffered saline vehicle rather the DNA vaccine. Sera were collected on days 0, 28, 56, 84, 140, 168, 196, 252 and 365 and evaluated for the presence of neutralizing antibodies by PUUV and HTNV pseudovirion neutralization assays (PsVNAs). Day 84 was also evaluated by a plaque reduction neutralization test (PRNT). Overall the PsVNA50 geometric mean titers (GMTs) and seropositivity rates among cohorts were similar. Cohort 3 exhibited the highest frequency of subjects that became seropositive to both PUUV and HTNV after vaccination, the highest peak GMT against both viruses, and the highest median titers against both viruses.
Jay Hooper; K. M. Paolino; K. Mills; S. Kwilas; M. Josleyn; M. Cohen; B. Somerville; M. Wisniewski; S. Norris; B. Hill; M. Sanchez-Lockhart; D. Hannaman; C. S. Schmaljohn. A Phase 2a Randomized, Double-Blind, Dose-Optimizing Study to Evaluate the Immunogenicity and Safety of a Bivalent DNA Vaccine for Hemorrhagic Fever with Renal Syndrome Delivered by Intramuscular Electroporation. Vaccines 2020, 8, 377 .
AMA StyleJay Hooper, K. M. Paolino, K. Mills, S. Kwilas, M. Josleyn, M. Cohen, B. Somerville, M. Wisniewski, S. Norris, B. Hill, M. Sanchez-Lockhart, D. Hannaman, C. S. Schmaljohn. A Phase 2a Randomized, Double-Blind, Dose-Optimizing Study to Evaluate the Immunogenicity and Safety of a Bivalent DNA Vaccine for Hemorrhagic Fever with Renal Syndrome Delivered by Intramuscular Electroporation. Vaccines. 2020; 8 (3):377.
Chicago/Turabian StyleJay Hooper; K. M. Paolino; K. Mills; S. Kwilas; M. Josleyn; M. Cohen; B. Somerville; M. Wisniewski; S. Norris; B. Hill; M. Sanchez-Lockhart; D. Hannaman; C. S. Schmaljohn. 2020. "A Phase 2a Randomized, Double-Blind, Dose-Optimizing Study to Evaluate the Immunogenicity and Safety of a Bivalent DNA Vaccine for Hemorrhagic Fever with Renal Syndrome Delivered by Intramuscular Electroporation." Vaccines 8, no. 3: 377.
Although Lloviu virus (LLOV) was discovered in the carcasses of insectivorous Schreiber’s Bent-winged bats in the caves of Northern Spain in 2002, its infectivity and pathogenicity remain unclear. We examined the seroprevalence of LLOV in potentially exposed Schreiber’s Bent-winged bats (n = 60), common serotine bats (n = 10) as controls, and humans (n = 22) using an immunoblot assay. We found antibodies against LLOV GP2 in all of Schreiber’s Bent-winged bats serum pools, but not in any of the common serotine bats and human pools tested. To confirm this seroreactivity, 52 serums were individually tested using Domain Programmable Arrays (DPA), a phage display based-system serology technique for profiling filovirus epitopes. A serological signature against different LLOV proteins was obtained in 19/52 samples tested (36.5%). The immunodominant response was in the majority specific to LLOV-unique epitopes, confirming that the serological response detected was to LLOV. To our knowledge, this is the first serological evidence of LLOV exposure in live captured Schreiber’s Bent-winged bats, dissociating LLOV circulation as the cause of the previously reported die-offs.
Eva Ramírez De Arellano; Mariano Sanchez-Lockhart; Maria J. Perteguer; Maggie Bartlett; Marta Ortiz; Pamela Campioli; Ana Hernández; Jeanette Gonzalez; Karla Garcia; Manuel Ramos; Miguel Ángel Jiménez-Clavero; Antonio Tenorio; Mª Paz Sánchez-Seco; Félix González; Juan Emilio Echevarría; Gustavo Palacios; Anabel Negredo. First Evidence of Antibodies Against Lloviu Virus in Schreiber’s Bent-Winged Insectivorous Bats Demonstrate a Wide Circulation of the Virus in Spain. Viruses 2019, 11, 360 .
AMA StyleEva Ramírez De Arellano, Mariano Sanchez-Lockhart, Maria J. Perteguer, Maggie Bartlett, Marta Ortiz, Pamela Campioli, Ana Hernández, Jeanette Gonzalez, Karla Garcia, Manuel Ramos, Miguel Ángel Jiménez-Clavero, Antonio Tenorio, Mª Paz Sánchez-Seco, Félix González, Juan Emilio Echevarría, Gustavo Palacios, Anabel Negredo. First Evidence of Antibodies Against Lloviu Virus in Schreiber’s Bent-Winged Insectivorous Bats Demonstrate a Wide Circulation of the Virus in Spain. Viruses. 2019; 11 (4):360.
Chicago/Turabian StyleEva Ramírez De Arellano; Mariano Sanchez-Lockhart; Maria J. Perteguer; Maggie Bartlett; Marta Ortiz; Pamela Campioli; Ana Hernández; Jeanette Gonzalez; Karla Garcia; Manuel Ramos; Miguel Ángel Jiménez-Clavero; Antonio Tenorio; Mª Paz Sánchez-Seco; Félix González; Juan Emilio Echevarría; Gustavo Palacios; Anabel Negredo. 2019. "First Evidence of Antibodies Against Lloviu Virus in Schreiber’s Bent-Winged Insectivorous Bats Demonstrate a Wide Circulation of the Virus in Spain." Viruses 11, no. 4: 360.
Summary Background The 2018 Ebola virus disease (EVD) outbreak in Équateur Province, Democratic Republic of the Congo, began on May 8, and was declared over on July 24; it resulted in 54 documented cases and 33 deaths. We did a retrospective genomic characterisation of the outbreak and assessed potential therapeutic agents and vaccine (medical countermeasures). Methods We used target-enrichment sequencing to produce Ebola virus genomes from samples obtained in the 2018 Équateur Province outbreak. Combining these genomes with genomes associated with known outbreaks from GenBank, we constructed a maximum-likelihood phylogenetic tree. In-silico analyses were used to assess potential mismatches between the outbreak strain and the probes and primers of diagnostic assays and the antigenic sites of the experimental rVSVΔG-ZEBOV-GP vaccine and therapeutics. An in-vitro flow cytometry assay was used to assess the binding capability of the individual components of the monoclonal antibody cocktail ZMapp. Findings A targeted sequencing approach produced 16 near-complete genomes. Phylogenetic analysis of these genomes and 1011 genomes from GenBank revealed a distinct cluster, confirming a new Ebola virus variant, for which we propose the name "Tumba". This new variant appears to have evolved at a slower rate than other Ebola virus variants (0·69 × 10−3 substitutions per site per year with "Tumba" vs 1·06 × 10−3 substitutions per site per year without "Tumba"). We found few sequence mismatches in the assessed assay target regions and antigenic sites. We identified nine amino acid changes in the Ebola virus surface glycoprotein, of which one resulted in reduced binding of the 13C6 antibody within the ZMapp cocktail. Interpretation Retrospectively, we show the feasibility of using genomics to rapidly characterise a new Ebola virus variant within the timeframe of an outbreak. Phylogenetic analysis provides further indications that these variants are evolving at differing rates. Rapid in-silico analyses can direct in-vitro experiments to quickly assess medical countermeasures. Funding Defense Biological Product Assurance Office.
Placide Mbala-Kingebeni; Catherine Pratt; Michael Wiley; Moussa M Diagne; Sheila Makiala-Mandanda; Amuri Aziza; Nicholas Di Paola; Joseph A Chitty; Mamadou Diop; Ahidjo Ayouba; Nicole Vidal; Ousmane Faye; Oumar Faye; Stormy Karhemere; Aaron Aruna; Justus Nsio; Felix Mulangu; Daniel Mukadi; Patrick Mukadi; John Kombe; Anastasie Mulumba; Sophie Duraffour; Jacques Likofata; Elisabeth Pukuta; Katie Caviness; Maggie L Bartlett; Jeanette Gonzalez; Timothy Minogue; Shanmuga Sozhamannan; Stephen M Gross; Gary P Schroth; Jens H Kuhn; Eric F Donaldson; Eric Delaporte; Mariano Sanchez-Lockhart; Martine Peeters; Jean-Jacques Muyembe-Tamfum; Amadou Alpha Sall; Gustavo Palacios; Steve Ahuka-Mundeke. 2018 Ebola virus disease outbreak in Équateur Province, Democratic Republic of the Congo: a retrospective genomic characterisation. The Lancet Infectious Diseases 2019, 19, 641 -647.
AMA StylePlacide Mbala-Kingebeni, Catherine Pratt, Michael Wiley, Moussa M Diagne, Sheila Makiala-Mandanda, Amuri Aziza, Nicholas Di Paola, Joseph A Chitty, Mamadou Diop, Ahidjo Ayouba, Nicole Vidal, Ousmane Faye, Oumar Faye, Stormy Karhemere, Aaron Aruna, Justus Nsio, Felix Mulangu, Daniel Mukadi, Patrick Mukadi, John Kombe, Anastasie Mulumba, Sophie Duraffour, Jacques Likofata, Elisabeth Pukuta, Katie Caviness, Maggie L Bartlett, Jeanette Gonzalez, Timothy Minogue, Shanmuga Sozhamannan, Stephen M Gross, Gary P Schroth, Jens H Kuhn, Eric F Donaldson, Eric Delaporte, Mariano Sanchez-Lockhart, Martine Peeters, Jean-Jacques Muyembe-Tamfum, Amadou Alpha Sall, Gustavo Palacios, Steve Ahuka-Mundeke. 2018 Ebola virus disease outbreak in Équateur Province, Democratic Republic of the Congo: a retrospective genomic characterisation. The Lancet Infectious Diseases. 2019; 19 (6):641-647.
Chicago/Turabian StylePlacide Mbala-Kingebeni; Catherine Pratt; Michael Wiley; Moussa M Diagne; Sheila Makiala-Mandanda; Amuri Aziza; Nicholas Di Paola; Joseph A Chitty; Mamadou Diop; Ahidjo Ayouba; Nicole Vidal; Ousmane Faye; Oumar Faye; Stormy Karhemere; Aaron Aruna; Justus Nsio; Felix Mulangu; Daniel Mukadi; Patrick Mukadi; John Kombe; Anastasie Mulumba; Sophie Duraffour; Jacques Likofata; Elisabeth Pukuta; Katie Caviness; Maggie L Bartlett; Jeanette Gonzalez; Timothy Minogue; Shanmuga Sozhamannan; Stephen M Gross; Gary P Schroth; Jens H Kuhn; Eric F Donaldson; Eric Delaporte; Mariano Sanchez-Lockhart; Martine Peeters; Jean-Jacques Muyembe-Tamfum; Amadou Alpha Sall; Gustavo Palacios; Steve Ahuka-Mundeke. 2019. "2018 Ebola virus disease outbreak in Équateur Province, Democratic Republic of the Congo: a retrospective genomic characterisation." The Lancet Infectious Diseases 19, no. 6: 641-647.
Summary Background The real-time generation of information about pathogen genomes has become a vital goal for transmission analysis and characterisation in rapid outbreak responses. In response to the recently established genomic capacity in the Democratic Republic of the Congo, we explored the real-time generation of genomic information at the start of the 2018 Ebola virus disease (EVD) outbreak in North Kivu Province. Methods We used targeted-enrichment sequencing to produce two coding-complete Ebola virus genomes 5 days after declaration of the EVD outbreak in North Kivu. Subsequent sequencing efforts yielded an additional 46 genomes. Genomic information was used to assess early transmission, medical countermeasures, and evolution of Ebola virus. Findings The genomic information demonstrated that the EVD outbreak in the North Kivu and Ituri Provinces was distinct from the 2018 EVD outbreak in Équateur Province of the Democratic Republic of the Congo. Primer and probe mismatches to Ebola virus were identified in silico for all deployed diagnostic PCR assays, with the exception of the Cepheid GeneXpert GP assay. Interpretation The first two coding-complete genomes provided actionable information in real-time for the deployment of the rVSVΔG-ZEBOV-GP Ebola virus envelope glycoprotein vaccine, available therapeutics, and sequence-based diagnostic assays. Based on the mutations identified in the Ebola virus surface glycoprotein (GP12) observed in all 48 genomes, deployed monoclonal antibody therapeutics (mAb114 and ZMapp) should be efficacious against the circulating Ebola virus variant. Rapid Ebola virus genomic characterisation should be included in routine EVD outbreak response procedures to ascertain efficacy of medical countermeasures. Funding Defense Biological Product Assurance Office.
Placide Mbala-Kingebeni; Amuri Aziza; Nicholas Di Paola; Michael Wiley; Sheila Makiala-Mandanda; Katie Caviness; Catherine Pratt; Jason T Ladner; Jeffrey R Kugelman; Karla Prieto; Joseph A Chitty; Peter A Larson; Brett Beitzel; Ahidjo Ayouba; Nicole Vidal; Stomy Karhemere; Mamadou Diop; Moussa M Diagne; Martin Faye; Ousmane Faye; Aaron Aruna; Justus Nsio; Felix Mulangu; Daniel Mukadi; Patrick Mukadi; John Kombe; Anastasie Mulumba; Christian-Julian Villabona-Arenas; Elisabeth Pukuta; Jeanette Gonzalez; Maggie L Bartlett; Shanmuga Sozhamannan; Stephen M Gross; Gary P Schroth; Roger Tim; Junhua J Zhao; Jens H Kuhn; Boubacar Diallo; Michel Yao; Ibrahima S Fall; Bathe Ndjoloko; Mathias Mossoko; Audrey Lacroix; Eric Delaporte; Mariano Sanchez-Lockhart; Amadou A Sall; Jean-Jacques Muyembe-Tamfum; Martine Peeters; Gustavo Palacios; Steve Ahuka-Mundeke. Medical countermeasures during the 2018 Ebola virus disease outbreak in the North Kivu and Ituri Provinces of the Democratic Republic of the Congo: a rapid genomic assessment. The Lancet Infectious Diseases 2019, 19, 648 -657.
AMA StylePlacide Mbala-Kingebeni, Amuri Aziza, Nicholas Di Paola, Michael Wiley, Sheila Makiala-Mandanda, Katie Caviness, Catherine Pratt, Jason T Ladner, Jeffrey R Kugelman, Karla Prieto, Joseph A Chitty, Peter A Larson, Brett Beitzel, Ahidjo Ayouba, Nicole Vidal, Stomy Karhemere, Mamadou Diop, Moussa M Diagne, Martin Faye, Ousmane Faye, Aaron Aruna, Justus Nsio, Felix Mulangu, Daniel Mukadi, Patrick Mukadi, John Kombe, Anastasie Mulumba, Christian-Julian Villabona-Arenas, Elisabeth Pukuta, Jeanette Gonzalez, Maggie L Bartlett, Shanmuga Sozhamannan, Stephen M Gross, Gary P Schroth, Roger Tim, Junhua J Zhao, Jens H Kuhn, Boubacar Diallo, Michel Yao, Ibrahima S Fall, Bathe Ndjoloko, Mathias Mossoko, Audrey Lacroix, Eric Delaporte, Mariano Sanchez-Lockhart, Amadou A Sall, Jean-Jacques Muyembe-Tamfum, Martine Peeters, Gustavo Palacios, Steve Ahuka-Mundeke. Medical countermeasures during the 2018 Ebola virus disease outbreak in the North Kivu and Ituri Provinces of the Democratic Republic of the Congo: a rapid genomic assessment. The Lancet Infectious Diseases. 2019; 19 (6):648-657.
Chicago/Turabian StylePlacide Mbala-Kingebeni; Amuri Aziza; Nicholas Di Paola; Michael Wiley; Sheila Makiala-Mandanda; Katie Caviness; Catherine Pratt; Jason T Ladner; Jeffrey R Kugelman; Karla Prieto; Joseph A Chitty; Peter A Larson; Brett Beitzel; Ahidjo Ayouba; Nicole Vidal; Stomy Karhemere; Mamadou Diop; Moussa M Diagne; Martin Faye; Ousmane Faye; Aaron Aruna; Justus Nsio; Felix Mulangu; Daniel Mukadi; Patrick Mukadi; John Kombe; Anastasie Mulumba; Christian-Julian Villabona-Arenas; Elisabeth Pukuta; Jeanette Gonzalez; Maggie L Bartlett; Shanmuga Sozhamannan; Stephen M Gross; Gary P Schroth; Roger Tim; Junhua J Zhao; Jens H Kuhn; Boubacar Diallo; Michel Yao; Ibrahima S Fall; Bathe Ndjoloko; Mathias Mossoko; Audrey Lacroix; Eric Delaporte; Mariano Sanchez-Lockhart; Amadou A Sall; Jean-Jacques Muyembe-Tamfum; Martine Peeters; Gustavo Palacios; Steve Ahuka-Mundeke. 2019. "Medical countermeasures during the 2018 Ebola virus disease outbreak in the North Kivu and Ituri Provinces of the Democratic Republic of the Congo: a rapid genomic assessment." The Lancet Infectious Diseases 19, no. 6: 648-657.
We generated genome sequences from 218 cases of Ebola virus disease (EVD) in Sierra Leone (SLE) during 2014–2015 to complement available datasets, particularly by including cases from a period of low sequence coverage during peak transmission of Ebola virus (EBOV) in the highly-affected Western Area division of SLE. The combined dataset was utilized to produce phylogenetic and phylodynamic inferences, to study sink–source dynamics and virus dispersal from highly-populated transmission hotspots. We identified four districts in SLE where EBOV was introduced and transmission occurred without onward exportation to other districts. We also identified six districts that substantially contributed to the dispersal of the virus and prolonged the EVD outbreak: five of these served as major hubs, with lots of movement in and out, and one acted primarily as a source, exporting the virus to other areas of the country. Positive correlations between case numbers, inter-district transition events, and district population sizes reaffirm that population size was a driver of EBOV transmission dynamics in SLE. The data presented here confirm the role of urban hubs in virus dispersal and of a delayed laboratory response in the expansion and perpetuation of the EVD outbreak in SLE.
Petrus Jansen Van Vuren; Jason T. Ladner; Antoinette A. Grobbelaar; Michael Wiley; Sean Lovett; Mushal Allam; Arshad Ismail; Chantel Le Roux; Jacqueline Weyer; Naazneen Moolla; Nadia Storm; Joe Kgaladi; Mariano Sanchez-Lockhart; Ousman Conteh; Gustavo Palacios; Janusz T. Paweska. Phylodynamic Analysis of Ebola Virus Disease Transmission in Sierra Leone. Viruses 2019, 11, 71 .
AMA StylePetrus Jansen Van Vuren, Jason T. Ladner, Antoinette A. Grobbelaar, Michael Wiley, Sean Lovett, Mushal Allam, Arshad Ismail, Chantel Le Roux, Jacqueline Weyer, Naazneen Moolla, Nadia Storm, Joe Kgaladi, Mariano Sanchez-Lockhart, Ousman Conteh, Gustavo Palacios, Janusz T. Paweska. Phylodynamic Analysis of Ebola Virus Disease Transmission in Sierra Leone. Viruses. 2019; 11 (1):71.
Chicago/Turabian StylePetrus Jansen Van Vuren; Jason T. Ladner; Antoinette A. Grobbelaar; Michael Wiley; Sean Lovett; Mushal Allam; Arshad Ismail; Chantel Le Roux; Jacqueline Weyer; Naazneen Moolla; Nadia Storm; Joe Kgaladi; Mariano Sanchez-Lockhart; Ousman Conteh; Gustavo Palacios; Janusz T. Paweska. 2019. "Phylodynamic Analysis of Ebola Virus Disease Transmission in Sierra Leone." Viruses 11, no. 1: 71.
The Egyptian rousette bat (ERB) is the only known Marburg virus (MARV) reservoir host. ERBs develop a productive MARV infection with low viremia and shedding but no overt disease, suggesting this virus is efficiently controlled by ERB antiviral responses. This dynamic would contrast with humans, where MARV-mediated interferon (IFN) antagonism early in infection is thought to contribute to the severe, often fatal disease. The newly-annotated ERB genome and transcriptome have now enabled us to use a custom-designed NanoString nCounter ERB CodeSet in conjunction with RNA-seq to investigate responses in a MARV-infected ERB cell line. Both transcriptomic platforms correlated well and showed that MARV inhibited the antiviral program in ERB cells, while an IFN antagonism-impaired MARV was less efficient at suppressing the response gene induction, phenotypes previously reported for primate cells. Interestingly, and despite the expansion of IFN loci in the ERB genome, neither MARV showed specific induction of almost any IFN gene. However, we detected an upregulation of putative, unannotated ERB antiviral paralogs, as well as an elevated basal expression in uninfected ERB cells of key antiviral genes.
Catherine E. Arnold; Jonathan C. Guito; Louis A. Altamura; Sean P. Lovett; Elyse R. Nagle; Gustavo F. Palacios; Mariano Sanchez-Lockhart; Jonathan S. Towner. Transcriptomics Reveal Antiviral Gene Induction in the Egyptian Rousette Bat Is Antagonized In Vitro by Marburg Virus Infection. Viruses 2018, 10, 607 .
AMA StyleCatherine E. Arnold, Jonathan C. Guito, Louis A. Altamura, Sean P. Lovett, Elyse R. Nagle, Gustavo F. Palacios, Mariano Sanchez-Lockhart, Jonathan S. Towner. Transcriptomics Reveal Antiviral Gene Induction in the Egyptian Rousette Bat Is Antagonized In Vitro by Marburg Virus Infection. Viruses. 2018; 10 (11):607.
Chicago/Turabian StyleCatherine E. Arnold; Jonathan C. Guito; Louis A. Altamura; Sean P. Lovett; Elyse R. Nagle; Gustavo F. Palacios; Mariano Sanchez-Lockhart; Jonathan S. Towner. 2018. "Transcriptomics Reveal Antiviral Gene Induction in the Egyptian Rousette Bat Is Antagonized In Vitro by Marburg Virus Infection." Viruses 10, no. 11: 607.
Summary Development of an effective vaccine became a worldwide priority after the devastating 2013–2016 Ebola disease outbreak. To qualitatively profile the humoral response against advanced filovirus vaccine candidates, we developed Domain Programmable Arrays (DPA), a systems serology platform to identify epitopes targeted after vaccination or filovirus infection. We optimized the assay using a panel of well-characterized monoclonal antibodies. After optimization, we utilized the system to longitudinally characterize the immunoglobulin (Ig) isotype-specific responses in non-human primates vaccinated with rVSV-ΔG-EBOV-glycoprotein (GP). Strikingly, we observed that, although the IgM response was directed against epitopes over the whole GP, the IgG and IgA responses were almost exclusively directed against the mucin-like domain (MLD) of the glycan cap. Further research will be needed to characterize this possible biased IgG and IgA response toward the MLD, but the results corroborate that DPA is a valuable tool to qualitatively measure the humoral response after vaccination.
Mariano Sanchez-Lockhart; Daniel S. Reyes; Jeanette C. Gonzalez; Karla Y. Garcia; Erika C. Villa; Bradley P. Pfeffer; John C. Trefry; Jeffrey R. Kugelman; Margaret Louise Pitt; Gustavo F. Palacios. Qualitative Profiling of the Humoral Immune Response Elicited by rVSV-ΔG-EBOV-GP Using a Systems Serology Assay, Domain Programmable Arrays. Cell Reports 2018, 24, 1050 -1059.e5.
AMA StyleMariano Sanchez-Lockhart, Daniel S. Reyes, Jeanette C. Gonzalez, Karla Y. Garcia, Erika C. Villa, Bradley P. Pfeffer, John C. Trefry, Jeffrey R. Kugelman, Margaret Louise Pitt, Gustavo F. Palacios. Qualitative Profiling of the Humoral Immune Response Elicited by rVSV-ΔG-EBOV-GP Using a Systems Serology Assay, Domain Programmable Arrays. Cell Reports. 2018; 24 (4):1050-1059.e5.
Chicago/Turabian StyleMariano Sanchez-Lockhart; Daniel S. Reyes; Jeanette C. Gonzalez; Karla Y. Garcia; Erika C. Villa; Bradley P. Pfeffer; John C. Trefry; Jeffrey R. Kugelman; Margaret Louise Pitt; Gustavo F. Palacios. 2018. "Qualitative Profiling of the Humoral Immune Response Elicited by rVSV-ΔG-EBOV-GP Using a Systems Serology Assay, Domain Programmable Arrays." Cell Reports 24, no. 4: 1050-1059.e5.
Summary Bats harbor many viruses asymptomatically, including several notorious for causing extreme virulence in humans. To identify differences between antiviral mechanisms in humans and bats, we sequenced, assembled, and analyzed the genome of Rousettus aegyptiacus, a natural reservoir of Marburg virus and the only known reservoir for any filovirus. We found an expanded and diversified KLRC/KLRD family of natural killer cell receptors, MHC class I genes, and type I interferons, which dramatically differ from their functional counterparts in other mammals. Such concerted evolution of key components of bat immunity is strongly suggestive of novel modes of antiviral defense. An evaluation of the theoretical function of these genes suggests that an inhibitory immune state may exist in bats. Based on our findings, we hypothesize that tolerance of viral infection, rather than enhanced potency of antiviral defenses, may be a key mechanism by which bats asymptomatically host viruses that are pathogenic in humans.
Stephanie S. Pavlovich; Sean P. Lovett; Galina Koroleva; Jonathan C. Guito; Catherine Arnold; Elyse R. Nagle; Kirsten Kulcsar; Albert Lee; Françoise Thibaud-Nissen; Adam Hume; Elke Muhlberger; Luke S. Uebelhoer; Jonathan S. Towner; Raul Rabadan; Mariano Sanchez-Lockhart; Thomas B. Kepler; Gustavo Palacios. The Egyptian Rousette Genome Reveals Unexpected Features of Bat Antiviral Immunity. Cell 2018, 173, 1098 -1110.e18.
AMA StyleStephanie S. Pavlovich, Sean P. Lovett, Galina Koroleva, Jonathan C. Guito, Catherine Arnold, Elyse R. Nagle, Kirsten Kulcsar, Albert Lee, Françoise Thibaud-Nissen, Adam Hume, Elke Muhlberger, Luke S. Uebelhoer, Jonathan S. Towner, Raul Rabadan, Mariano Sanchez-Lockhart, Thomas B. Kepler, Gustavo Palacios. The Egyptian Rousette Genome Reveals Unexpected Features of Bat Antiviral Immunity. Cell. 2018; 173 (5):1098-1110.e18.
Chicago/Turabian StyleStephanie S. Pavlovich; Sean P. Lovett; Galina Koroleva; Jonathan C. Guito; Catherine Arnold; Elyse R. Nagle; Kirsten Kulcsar; Albert Lee; Françoise Thibaud-Nissen; Adam Hume; Elke Muhlberger; Luke S. Uebelhoer; Jonathan S. Towner; Raul Rabadan; Mariano Sanchez-Lockhart; Thomas B. Kepler; Gustavo Palacios. 2018. "The Egyptian Rousette Genome Reveals Unexpected Features of Bat Antiviral Immunity." Cell 173, no. 5: 1098-1110.e18.
We performed epitope mapping studies on the major surface glycoprotein (GP) of Ebola virus (EBOV) using Chemically Linked Peptides on Scaffolds (CLIPS), which form linear and potential conformational epitopes. This method identified monoclonal antibody epitopes and predicted additional epitopes recognized by antibodies in polyclonal sera from animals experimentally vaccinated against or infected with EBOV. Using the information obtained along with structural modeling to predict epitope accessibility, we then constructed 2 DNA vaccines encoding immunodominant and subdominant epitopes predicted to be accessible on EBOV GP. Although a construct designed to produce a membrane-bound oligopeptide was poorly immunogenic, a construct generating a secreted oligopeptide elicited strong antibody responses in mice. When this construct was administered as a boost to a DNA vaccine expressing the complete EBOV GP gene, the resultant antibody response was focused largely toward the less immunodominant epitopes in the oligopeptide. Taken together, the results of this work suggest a utility for this method for immune focusing of antibody responses elicited by vaccination.
Daniel A. J. Mitchell; Lesley C. Dupuy; Mariano Sanchez-Lockhart; Gustavo Palacios; Jw Back; Katya Shimanovskaya; Sidhartha Chaudhury; Daniel R. Ripoll; Anders Wallqvist; Connie S. Schmaljohn. Epitope mapping of Ebola virus dominant and subdominant glycoprotein epitopes facilitates construction of an epitope-based DNA vaccine able to focus the antibody response in mice. Human Vaccines & Immunotherapeutics 2017, 13, 2883 -2893.
AMA StyleDaniel A. J. Mitchell, Lesley C. Dupuy, Mariano Sanchez-Lockhart, Gustavo Palacios, Jw Back, Katya Shimanovskaya, Sidhartha Chaudhury, Daniel R. Ripoll, Anders Wallqvist, Connie S. Schmaljohn. Epitope mapping of Ebola virus dominant and subdominant glycoprotein epitopes facilitates construction of an epitope-based DNA vaccine able to focus the antibody response in mice. Human Vaccines & Immunotherapeutics. 2017; 13 (12):2883-2893.
Chicago/Turabian StyleDaniel A. J. Mitchell; Lesley C. Dupuy; Mariano Sanchez-Lockhart; Gustavo Palacios; Jw Back; Katya Shimanovskaya; Sidhartha Chaudhury; Daniel R. Ripoll; Anders Wallqvist; Connie S. Schmaljohn. 2017. "Epitope mapping of Ebola virus dominant and subdominant glycoprotein epitopes facilitates construction of an epitope-based DNA vaccine able to focus the antibody response in mice." Human Vaccines & Immunotherapeutics 13, no. 12: 2883-2893.
Genome sequencing of Zika virus samples from infected patients and Aedes aegypti mosquitoes in Florida shows that the virus was probably introduced into the United States on multiple occasions, and that the Caribbean is the most likely source. Three papers in this issue present a wealth of new Zika virus (ZIKV) genome sequences and further insights into the genetic epidemiology of ZIKV. Nathan Grubaugh et al. provide 39 new ZIKV genome sequences from infected patients and Aedes aegypti mosquitoes in Florida. Phylogenetic analysis suggests that the virus has been introduced on multiple separate occasions, probably linked to travel from the Caribbean. They find a low probability of long-term persistence of ZIKV transmission chains within Florida, suggesting that the potential for future ZIKV outbreaks there will depend on transmission dynamics in the Americas. Nuno Faria et al. and Hayden Metsky et al. reconstruct the spread of ZIKV in Brazil and the Americas. Faria et al. provide 54 new ZIKV genomes, several sequenced in real time in a mobile genomics laboratory. They trace the spatial origins and spread of ZIKV in Brazil and the Americas and date the timing of the international spread of ZIKV from Brazil. They find that northeast Brazil had a crucial role in the establishment of the epidemic and the spread of the virus within Brazil and the Americas. Metsky et al. generate 110 ZIKV genomes from clinical and mosquito samples from ten regions. They also see rapid expansion of the epidemic within Brazil and multiple introductions to other geographic areas. In agreement with Faria et al., they find that ZIKV circulated unobserved for many months before transmission was detected. Metsky et al. additionally describe ZIKV evolution and discuss how the accumulation of mutations might affect the performance of diagnostic tests in the future. Zika virus (ZIKV) is causing an unprecedented epidemic linked to severe congenital abnormalities1,2. In July 2016, mosquito-borne ZIKV transmission was reported in the continental United States; since then, hundreds of locally acquired infections have been reported in Florida3,4. To gain insights into the timing, source, and likely route(s) of ZIKV introduction, we tracked the virus from its first detection in Florida by sequencing ZIKV genomes from infected patients and Aedes aegypti mosquitoes. We show that at least 4 introductions, but potentially as many as 40, contributed to the outbreak in Florida and that local transmission is likely to have started in the spring of 2016—several months before its initial detection. By analysing surveillance and genetic data, we show that ZIKV moved among transmission zones in Miami. Our analyses show that most introductions were linked to the Caribbean, a finding corroborated by the high incidence rates and traffic volumes from the region into the Miami area. Our study provides an understanding of how ZIKV initiates transmission in new regions.
Nathan Grubaugh; Jason T. Ladner; Moritz U. G. Kraemer; Gytis Dudas; Amanda L. Tan; Karthik Gangavarapu; Michael Wiley; Stephen White; Julien Thézé; Diogo Magnani; Karla Prieto; Daniel Reyes; Andrea M. Bingham; Lauren Paul; Refugio Robles-Sikisaka; Glenn Oliveira; Darryl Pronty; Carolyn M. Barcellona; Hayden C. Metsky; Mary Lynn Baniecki; Kayla G. Barnes; Bridget Chak; Catherine A. Freije; Adrianne Gladden-Young; Andreas Gnirke; Cynthia Luo; Bronwyn MacInnis; Christian B. Matranga; Daniel J. Park; James Qu; Stephen F. Schaffner; Christopher Tomkins-Tinch; Kendra L. West; Sarah M. Winnicki; Shirlee Wohl; Nathan L. Yozwiak; Joshua Quick; Joseph R. Fauver; Kamran Khan; Shannon E. Brent; Robert C. Reiner Jr; Paola N. Lichtenberger; Michael J. Ricciardi; Varian K. Bailey; David I. Watkins; Marshall R. Cone; Edgar W. Kopp; Kelly N. Hogan; Andrew C. Cannons; Reynald Jean; Andrew J. Monaghan; Robert Garry; Nicholas Loman; Nuno Rodrigues Faria; Mario C. Porcelli; Chalmers Vasquez; Elyse R. Nagle; Derek A. T. Cummings; Danielle Stanek; Andrew Rambaut; Mariano Sanchez-Lockhart; Pardis C. Sabeti; Leah D. Gillis; Scott F. Michael; Trevor Bedford; Oliver Pybus; Sharon Isern; Gustavo Palacios; Kristian G. Andersen. Genomic epidemiology reveals multiple introductions of Zika virus into the United States. Nature 2017, 546, 401 -405.
AMA StyleNathan Grubaugh, Jason T. Ladner, Moritz U. G. Kraemer, Gytis Dudas, Amanda L. Tan, Karthik Gangavarapu, Michael Wiley, Stephen White, Julien Thézé, Diogo Magnani, Karla Prieto, Daniel Reyes, Andrea M. Bingham, Lauren Paul, Refugio Robles-Sikisaka, Glenn Oliveira, Darryl Pronty, Carolyn M. Barcellona, Hayden C. Metsky, Mary Lynn Baniecki, Kayla G. Barnes, Bridget Chak, Catherine A. Freije, Adrianne Gladden-Young, Andreas Gnirke, Cynthia Luo, Bronwyn MacInnis, Christian B. Matranga, Daniel J. Park, James Qu, Stephen F. Schaffner, Christopher Tomkins-Tinch, Kendra L. West, Sarah M. Winnicki, Shirlee Wohl, Nathan L. Yozwiak, Joshua Quick, Joseph R. Fauver, Kamran Khan, Shannon E. Brent, Robert C. Reiner Jr, Paola N. Lichtenberger, Michael J. Ricciardi, Varian K. Bailey, David I. Watkins, Marshall R. Cone, Edgar W. Kopp, Kelly N. Hogan, Andrew C. Cannons, Reynald Jean, Andrew J. Monaghan, Robert Garry, Nicholas Loman, Nuno Rodrigues Faria, Mario C. Porcelli, Chalmers Vasquez, Elyse R. Nagle, Derek A. T. Cummings, Danielle Stanek, Andrew Rambaut, Mariano Sanchez-Lockhart, Pardis C. Sabeti, Leah D. Gillis, Scott F. Michael, Trevor Bedford, Oliver Pybus, Sharon Isern, Gustavo Palacios, Kristian G. Andersen. Genomic epidemiology reveals multiple introductions of Zika virus into the United States. Nature. 2017; 546 (7658):401-405.
Chicago/Turabian StyleNathan Grubaugh; Jason T. Ladner; Moritz U. G. Kraemer; Gytis Dudas; Amanda L. Tan; Karthik Gangavarapu; Michael Wiley; Stephen White; Julien Thézé; Diogo Magnani; Karla Prieto; Daniel Reyes; Andrea M. Bingham; Lauren Paul; Refugio Robles-Sikisaka; Glenn Oliveira; Darryl Pronty; Carolyn M. Barcellona; Hayden C. Metsky; Mary Lynn Baniecki; Kayla G. Barnes; Bridget Chak; Catherine A. Freije; Adrianne Gladden-Young; Andreas Gnirke; Cynthia Luo; Bronwyn MacInnis; Christian B. Matranga; Daniel J. Park; James Qu; Stephen F. Schaffner; Christopher Tomkins-Tinch; Kendra L. West; Sarah M. Winnicki; Shirlee Wohl; Nathan L. Yozwiak; Joshua Quick; Joseph R. Fauver; Kamran Khan; Shannon E. Brent; Robert C. Reiner Jr; Paola N. Lichtenberger; Michael J. Ricciardi; Varian K. Bailey; David I. Watkins; Marshall R. Cone; Edgar W. Kopp; Kelly N. Hogan; Andrew C. Cannons; Reynald Jean; Andrew J. Monaghan; Robert Garry; Nicholas Loman; Nuno Rodrigues Faria; Mario C. Porcelli; Chalmers Vasquez; Elyse R. Nagle; Derek A. T. Cummings; Danielle Stanek; Andrew Rambaut; Mariano Sanchez-Lockhart; Pardis C. Sabeti; Leah D. Gillis; Scott F. Michael; Trevor Bedford; Oliver Pybus; Sharon Isern; Gustavo Palacios; Kristian G. Andersen. 2017. "Genomic epidemiology reveals multiple introductions of Zika virus into the United States." Nature 546, no. 7658: 401-405.
The 2013–2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic ‘gravity’ model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions. Finally, we reveal that this large epidemic was a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help to inform interventions in future epidemics. Frequent dispersal and short-lived local transmission clusters fuelled the 2013–2016 Ebola virus epidemic in Guinea, Liberia and Sierra Leone. Understanding how and why viruses spread during epidemics is crucial for planning how to prevent and respond to future threats. Andrew Rambaut and colleagues provide an overview of the genetic epidemiology of the 2013–2016 epidemic caused by Ebola virus in West Africa. By analysing more than 1,600 Ebola virus genomes, the authors determine the factors that were important in the spread of the epidemic and also explain why the virus did not spread into neighbouring countries.
Gytis Dudas; Luiz Max Carvalho; Trevor Bedford; Andrew J. Tatem; Guy Baele; Nuno R. Faria; Daniel J. Park; Jason T. Ladner; Armando Arias; Danny Asogun; Filip Bielejec; Sarah L. Caddy; Matthew Cotten; Jonathan D’Ambrozio; Simon Dellicour; Antonino Di Caro; Joseph W. Diclaro; Sophie Duraffour; Michael J. Elmore; Lawrence S. Fakoli; Ousmane Faye; Merle L. Gilbert; Sahr M. Gevao; Stephen Gire; Adrianne Gladden-Young; Andreas Gnirke; Augustine Goba; Donald S. Grant; Bart L. Haagmans; Julian A. Hiscox; Umaru Jah; Jeffrey R. Kugelman; Di Liu; Jia Lu; Christine M. Malboeuf; Suzanne Mate; David A. Matthews; Christian B. Matranga; Luke W. Meredith; James Qu; Joshua Quick; Suzan D. Pas; My V. T. Phan; Georgios Pollakis; Chantal B. Reusken; Mariano Sanchez-Lockhart; Stephen F. Schaffner; John S. Schieffelin; Rachel S. Sealfon; Etienne Simon-Loriere; Saskia L. Smits; Kilian Stoecker; Lucy Thorne; Ekaete Alice Tobin; Mohamed A. Vandi; Simon J. Watson; Kendra West; Shannon Whitmer; Michael R. Wiley; Sarah M. Winnicki; Shirlee Wohl; Roman Wölfel; Nathan L. Yozwiak; Kristian G. Andersen; Sylvia O. Blyden; Fatorma Bolay; Miles W. Carroll; Bernice Dahn; Boubacar Diallo; Pierre Formenty; Christophe Fraser; George F. Gao; Robert F. Garry; Ian Goodfellow; Stephan Günther; Christian T. Happi; Edward C. Holmes; Brima Kargbo; Sakoba Keïta; Paul Kellam; Marion P. G. Koopmans; Jens H. Kuhn; Nicholas J. Loman; N’Faly Magassouba; Dhamari Naidoo; Stuart T. Nichol; Tolbert Nyenswah; Gustavo Palacios; Oliver G. Pybus; Pardis C. Sabeti; Amadou Sall; Ute Ströher; Isatta Wurie; Marc A. Suchard; Philippe Lemey; Andrew Rambaut. Virus genomes reveal factors that spread and sustained the Ebola epidemic. Nature 2017, 544, 309 -315.
AMA StyleGytis Dudas, Luiz Max Carvalho, Trevor Bedford, Andrew J. Tatem, Guy Baele, Nuno R. Faria, Daniel J. Park, Jason T. Ladner, Armando Arias, Danny Asogun, Filip Bielejec, Sarah L. Caddy, Matthew Cotten, Jonathan D’Ambrozio, Simon Dellicour, Antonino Di Caro, Joseph W. Diclaro, Sophie Duraffour, Michael J. Elmore, Lawrence S. Fakoli, Ousmane Faye, Merle L. Gilbert, Sahr M. Gevao, Stephen Gire, Adrianne Gladden-Young, Andreas Gnirke, Augustine Goba, Donald S. Grant, Bart L. Haagmans, Julian A. Hiscox, Umaru Jah, Jeffrey R. Kugelman, Di Liu, Jia Lu, Christine M. Malboeuf, Suzanne Mate, David A. Matthews, Christian B. Matranga, Luke W. Meredith, James Qu, Joshua Quick, Suzan D. Pas, My V. T. Phan, Georgios Pollakis, Chantal B. Reusken, Mariano Sanchez-Lockhart, Stephen F. Schaffner, John S. Schieffelin, Rachel S. Sealfon, Etienne Simon-Loriere, Saskia L. Smits, Kilian Stoecker, Lucy Thorne, Ekaete Alice Tobin, Mohamed A. Vandi, Simon J. Watson, Kendra West, Shannon Whitmer, Michael R. Wiley, Sarah M. Winnicki, Shirlee Wohl, Roman Wölfel, Nathan L. Yozwiak, Kristian G. Andersen, Sylvia O. Blyden, Fatorma Bolay, Miles W. Carroll, Bernice Dahn, Boubacar Diallo, Pierre Formenty, Christophe Fraser, George F. Gao, Robert F. Garry, Ian Goodfellow, Stephan Günther, Christian T. Happi, Edward C. Holmes, Brima Kargbo, Sakoba Keïta, Paul Kellam, Marion P. G. Koopmans, Jens H. Kuhn, Nicholas J. Loman, N’Faly Magassouba, Dhamari Naidoo, Stuart T. Nichol, Tolbert Nyenswah, Gustavo Palacios, Oliver G. Pybus, Pardis C. Sabeti, Amadou Sall, Ute Ströher, Isatta Wurie, Marc A. Suchard, Philippe Lemey, Andrew Rambaut. Virus genomes reveal factors that spread and sustained the Ebola epidemic. Nature. 2017; 544 (7650):309-315.
Chicago/Turabian StyleGytis Dudas; Luiz Max Carvalho; Trevor Bedford; Andrew J. Tatem; Guy Baele; Nuno R. Faria; Daniel J. Park; Jason T. Ladner; Armando Arias; Danny Asogun; Filip Bielejec; Sarah L. Caddy; Matthew Cotten; Jonathan D’Ambrozio; Simon Dellicour; Antonino Di Caro; Joseph W. Diclaro; Sophie Duraffour; Michael J. Elmore; Lawrence S. Fakoli; Ousmane Faye; Merle L. Gilbert; Sahr M. Gevao; Stephen Gire; Adrianne Gladden-Young; Andreas Gnirke; Augustine Goba; Donald S. Grant; Bart L. Haagmans; Julian A. Hiscox; Umaru Jah; Jeffrey R. Kugelman; Di Liu; Jia Lu; Christine M. Malboeuf; Suzanne Mate; David A. Matthews; Christian B. Matranga; Luke W. Meredith; James Qu; Joshua Quick; Suzan D. Pas; My V. T. Phan; Georgios Pollakis; Chantal B. Reusken; Mariano Sanchez-Lockhart; Stephen F. Schaffner; John S. Schieffelin; Rachel S. Sealfon; Etienne Simon-Loriere; Saskia L. Smits; Kilian Stoecker; Lucy Thorne; Ekaete Alice Tobin; Mohamed A. Vandi; Simon J. Watson; Kendra West; Shannon Whitmer; Michael R. Wiley; Sarah M. Winnicki; Shirlee Wohl; Roman Wölfel; Nathan L. Yozwiak; Kristian G. Andersen; Sylvia O. Blyden; Fatorma Bolay; Miles W. Carroll; Bernice Dahn; Boubacar Diallo; Pierre Formenty; Christophe Fraser; George F. Gao; Robert F. Garry; Ian Goodfellow; Stephan Günther; Christian T. Happi; Edward C. Holmes; Brima Kargbo; Sakoba Keïta; Paul Kellam; Marion P. G. Koopmans; Jens H. Kuhn; Nicholas J. Loman; N’Faly Magassouba; Dhamari Naidoo; Stuart T. Nichol; Tolbert Nyenswah; Gustavo Palacios; Oliver G. Pybus; Pardis C. Sabeti; Amadou Sall; Ute Ströher; Isatta Wurie; Marc A. Suchard; Philippe Lemey; Andrew Rambaut. 2017. "Virus genomes reveal factors that spread and sustained the Ebola epidemic." Nature 544, no. 7650: 309-315.
Individual RNA viruses typically occur as populations of genomes that differ slightly from each other due to mutations introduced by the error-prone viral polymerase. Understanding the variability of RNA virus genome populations is critical for understanding virus evolution because individual mutant genomes may gain evolutionary selective advantages and give rise to dominant subpopulations, possibly even leading to the emergence of viruses resistant to medical countermeasures. Reverse transcription of virus genome populations followed by next-generation sequencing is the only available method to characterize variation for RNA viruses. However, both steps may lead to the introduction of artificial mutations, thereby skewing the data. To better understand how such errors are introduced during sample preparation, we determined and compared error baseline rates of five different sample preparation methods by analyzing in vitro transcribed Ebola virus RNA from an artificial plasmid-based system. These methods included: shotgun sequencing from plasmid DNA or in vitro transcribed RNA as a basic “no amplification” method, amplicon sequencing from the plasmid DNA or in vitro transcribed RNA as a “targeted” amplification method, sequence-independent single-primer amplification (SISPA) as a “random” amplification method, rolling circle reverse transcription sequencing (CirSeq) as an advanced “no amplification” method, and Illumina TruSeq RNA Access as a “targeted” enrichment method. The measured error frequencies indicate that RNA Access offers the best tradeoff between sensitivity and sample preparation error (1.4−5) of all compared methods.
Jeffrey R. Kugelman; Michael Wiley; Elyse R. Nagle; Daniel Reyes; Brad P. Pfeffer; Jens H. Kuhn; Mariano Sanchez-Lockhart; Gustavo F. Palacios. Error baseline rates of five sample preparation methods used to characterize RNA virus populations. PLOS ONE 2017, 12, e0171333 .
AMA StyleJeffrey R. Kugelman, Michael Wiley, Elyse R. Nagle, Daniel Reyes, Brad P. Pfeffer, Jens H. Kuhn, Mariano Sanchez-Lockhart, Gustavo F. Palacios. Error baseline rates of five sample preparation methods used to characterize RNA virus populations. PLOS ONE. 2017; 12 (2):e0171333.
Chicago/Turabian StyleJeffrey R. Kugelman; Michael Wiley; Elyse R. Nagle; Daniel Reyes; Brad P. Pfeffer; Jens H. Kuhn; Mariano Sanchez-Lockhart; Gustavo F. Palacios. 2017. "Error baseline rates of five sample preparation methods used to characterize RNA virus populations." PLOS ONE 12, no. 2: e0171333.
Cynomolgus macaques (Macaca fascicularis) have become an important animal model for biomedical research. In particular, it is the animal model of choice for the development of vaccine candidates associated with emerging dangerous pathogens. Despite their increasing importance as animal models, the cynomolgus macaque genome is not fully characterized, hindering molecular studies for this model. More importantly, the lack of knowledge about the immunoglobulin (IG) locus organization directly impacts the analysis of the humoral response in cynomolgus macaques. Recent advances in next generation sequencing (NGS) technologies to analyze IG repertoires open the opportunity to deeply characterize the humoral immune response. However, the IG locus organization for the animal is required to completely dissect IG repertoires. Here, we describe the localization and organization of the rearranging IG heavy (IGH) genes on chromosome 7 of the cynomolgus macaque draft genome. Our annotation comprises 108 functional genes which include 63 variable (IGHV), 38 diversity (IGHD), and 7 joining (IGHJ) genes. For validation, we provide RNA transcript data for most of the IGHV genes and all of the annotated IGHJ genes, as well as proteomic data to validate IGH constant genes. The description and annotation of the rearranging IGH genes for the cynomolgus macaques will significantly facilitate scientific research. This is particularly relevant to dissect the immune response during vaccination or infection with dangerous pathogens such as Ebola, Marburg and other emerging pathogens where non-human primate models play a significant role for countermeasure development.
Guo-Yun Yu; Suzanne Mate; Karla Garcia; Michael D. Ward; Ernst Brueggemann; Matthew Hall; Tara Kenny; Mariano Sanchez-Lockhart; Marie-Paule Lefranc; Gustavo Palacios. Cynomolgus macaque (Macaca fascicularis) immunoglobulin heavy chain locus description. Immunogenetics 2016, 68, 417 -428.
AMA StyleGuo-Yun Yu, Suzanne Mate, Karla Garcia, Michael D. Ward, Ernst Brueggemann, Matthew Hall, Tara Kenny, Mariano Sanchez-Lockhart, Marie-Paule Lefranc, Gustavo Palacios. Cynomolgus macaque (Macaca fascicularis) immunoglobulin heavy chain locus description. Immunogenetics. 2016; 68 (6-7):417-428.
Chicago/Turabian StyleGuo-Yun Yu; Suzanne Mate; Karla Garcia; Michael D. Ward; Ernst Brueggemann; Matthew Hall; Tara Kenny; Mariano Sanchez-Lockhart; Marie-Paule Lefranc; Gustavo Palacios. 2016. "Cynomolgus macaque (Macaca fascicularis) immunoglobulin heavy chain locus description." Immunogenetics 68, no. 6-7: 417-428.
On 29 June 2015, Liberia’s respite from Ebola virus disease (EVD) was interrupted for the second time by a renewed outbreak (“flare-up”) of seven confirmed cases. We demonstrate that, similar to the March 2015 flare-up associated with sexual transmission, this new flare-up was a reemergence of a Liberian transmission chain originating from a persistently infected source rather than a reintroduction from a reservoir or a neighboring country with active transmission. Although distinct, Ebola virus (EBOV) genomes from both flare-ups exhibit significantly low genetic divergence, indicating a reduced rate of EBOV evolution during persistent infection. Using this rate of change as a signature, we identified two additional EVD clusters that possibly arose from persistently infected sources. These findings highlight the risk of EVD flare-ups even after an outbreak is declared over.
David J. Blackley; Michael R. Wiley; Jason T. Ladner; Mosoka Fallah; Terrence Lo; Merle L. Gilbert; Christopher Gregory; Jonathan D’Ambrozio; Stewart Coulter; Suzanne Mate; Zephaniah Balogun; Jeffrey Kugelman; William Nwachukwu; Karla Prieto; Adolphus Yeiah; Fred Amegashie; Brian Kearney; Meagan Wisniewski; John Saindon; Gary Schroth; Lawrence Fakoli; Joseph W. Diclaro; Jens H. Kuhn; Lisa E. Hensley; Peter B. Jahrling; Ute Ströher; Stuart T. Nichol; Moses Massaquoi; Francis Kateh; Peter Clement; Alex Gasasira; Fatorma Bolay; Stephan S. Monroe; Andrew Rambaut; Mariano Sanchez-Lockhart; A. Scott Laney; Tolbert Nyenswah; Athalia Christie; Gustavo Palacios. Reduced evolutionary rate in reemerged Ebola virus transmission chains. Science Advances 2016, 2, e1600378 -1600378.
AMA StyleDavid J. Blackley, Michael R. Wiley, Jason T. Ladner, Mosoka Fallah, Terrence Lo, Merle L. Gilbert, Christopher Gregory, Jonathan D’Ambrozio, Stewart Coulter, Suzanne Mate, Zephaniah Balogun, Jeffrey Kugelman, William Nwachukwu, Karla Prieto, Adolphus Yeiah, Fred Amegashie, Brian Kearney, Meagan Wisniewski, John Saindon, Gary Schroth, Lawrence Fakoli, Joseph W. Diclaro, Jens H. Kuhn, Lisa E. Hensley, Peter B. Jahrling, Ute Ströher, Stuart T. Nichol, Moses Massaquoi, Francis Kateh, Peter Clement, Alex Gasasira, Fatorma Bolay, Stephan S. Monroe, Andrew Rambaut, Mariano Sanchez-Lockhart, A. Scott Laney, Tolbert Nyenswah, Athalia Christie, Gustavo Palacios. Reduced evolutionary rate in reemerged Ebola virus transmission chains. Science Advances. 2016; 2 (4):e1600378-1600378.
Chicago/Turabian StyleDavid J. Blackley; Michael R. Wiley; Jason T. Ladner; Mosoka Fallah; Terrence Lo; Merle L. Gilbert; Christopher Gregory; Jonathan D’Ambrozio; Stewart Coulter; Suzanne Mate; Zephaniah Balogun; Jeffrey Kugelman; William Nwachukwu; Karla Prieto; Adolphus Yeiah; Fred Amegashie; Brian Kearney; Meagan Wisniewski; John Saindon; Gary Schroth; Lawrence Fakoli; Joseph W. Diclaro; Jens H. Kuhn; Lisa E. Hensley; Peter B. Jahrling; Ute Ströher; Stuart T. Nichol; Moses Massaquoi; Francis Kateh; Peter Clement; Alex Gasasira; Fatorma Bolay; Stephan S. Monroe; Andrew Rambaut; Mariano Sanchez-Lockhart; A. Scott Laney; Tolbert Nyenswah; Athalia Christie; Gustavo Palacios. 2016. "Reduced evolutionary rate in reemerged Ebola virus transmission chains." Science Advances 2, no. 4: e1600378-1600378.
A suspected case of sexual transmission from a male survivor of Ebola virus disease (EVD) to his female partner (the patient in this report) occurred in Liberia in March 2015. Ebola virus (EBOV) genomes assembled from blood samples from the patient and a semen sample from the survivor were consistent with direct transmission. The genomes shared three substitutions that were absent from all other Western African EBOV sequences and that were distinct from the last documented transmission chain in Liberia before this case. Combined with epidemiologic data, the genomic analysis provides evidence of sexual transmission of EBOV and evidence of the persistence of infective EBOV in semen for 179 days or more after the onset of EVD. (Funded by the Defense Threat Reduction Agency and others.)
Suzanne E. Mate; Jeffrey R. Kugelman; Tolbert G. Nyenswah; Jason T. Ladner; Michael Wiley; Thierry Cordier-Lassalle; Athalia Christie; Gary P. Schroth; Stephen Gross; Gloria J. Davies-Wayne; Shivam A. Shinde; Ratnesh Murugan; Sonpon B. Sieh; Moses Badio; Lawrence Fakoli; Fahn Taweh; Emmie de Wit; Neeltje Van Doremalen; Vincent Munster; James Pettitt; Karla Prieto; Ben W. Humrighouse; Ute Ströher; Joseph W. DiClaro; Lisa Hensley; Randal Schoepp; David Safronetz; Joseph Fair; Jens H. Kuhn; David J. Blackley; A. Scott Laney; Desmond E. Williams; Terrence Lo; Alex Gasasira; Stuart T. Nichol; Pierre Formenty; Francis N. Kateh; Kevin M. De Cock; Fatorma Bolay; Mariano Sanchez-Lockhart; Gustavo Palacios. Molecular Evidence of Sexual Transmission of Ebola Virus. New England Journal of Medicine 2015, 373, 2448 -2454.
AMA StyleSuzanne E. Mate, Jeffrey R. Kugelman, Tolbert G. Nyenswah, Jason T. Ladner, Michael Wiley, Thierry Cordier-Lassalle, Athalia Christie, Gary P. Schroth, Stephen Gross, Gloria J. Davies-Wayne, Shivam A. Shinde, Ratnesh Murugan, Sonpon B. Sieh, Moses Badio, Lawrence Fakoli, Fahn Taweh, Emmie de Wit, Neeltje Van Doremalen, Vincent Munster, James Pettitt, Karla Prieto, Ben W. Humrighouse, Ute Ströher, Joseph W. DiClaro, Lisa Hensley, Randal Schoepp, David Safronetz, Joseph Fair, Jens H. Kuhn, David J. Blackley, A. Scott Laney, Desmond E. Williams, Terrence Lo, Alex Gasasira, Stuart T. Nichol, Pierre Formenty, Francis N. Kateh, Kevin M. De Cock, Fatorma Bolay, Mariano Sanchez-Lockhart, Gustavo Palacios. Molecular Evidence of Sexual Transmission of Ebola Virus. New England Journal of Medicine. 2015; 373 (25):2448-2454.
Chicago/Turabian StyleSuzanne E. Mate; Jeffrey R. Kugelman; Tolbert G. Nyenswah; Jason T. Ladner; Michael Wiley; Thierry Cordier-Lassalle; Athalia Christie; Gary P. Schroth; Stephen Gross; Gloria J. Davies-Wayne; Shivam A. Shinde; Ratnesh Murugan; Sonpon B. Sieh; Moses Badio; Lawrence Fakoli; Fahn Taweh; Emmie de Wit; Neeltje Van Doremalen; Vincent Munster; James Pettitt; Karla Prieto; Ben W. Humrighouse; Ute Ströher; Joseph W. DiClaro; Lisa Hensley; Randal Schoepp; David Safronetz; Joseph Fair; Jens H. Kuhn; David J. Blackley; A. Scott Laney; Desmond E. Williams; Terrence Lo; Alex Gasasira; Stuart T. Nichol; Pierre Formenty; Francis N. Kateh; Kevin M. De Cock; Fatorma Bolay; Mariano Sanchez-Lockhart; Gustavo Palacios. 2015. "Molecular Evidence of Sexual Transmission of Ebola Virus." New England Journal of Medicine 373, no. 25: 2448-2454.
The Egyptian Rousette bat (Rousettus aegyptiacus), a common fruit bat species found throughout Africa and the Middle East, was recently identified as a natural reservoir host of Marburg virus. With Ebola virus, Marburg virus is a member of the family Filoviridae that causes severe hemorrhagic fever disease in humans and nonhuman primates, but results in little to no pathological consequences in bats. Understanding host-pathogen interactions within reservoir host species and how it differs from hosts that experience severe disease is an important aspect of evaluating viral pathogenesis and developing novel therapeutics and methods of prevention. Progress in studying bat reservoir host responses to virus infection is hampered by the lack of host-specific reagents required for immunological studies. In order to establish a basis for the design of reagents, we sequenced, assembled, and annotated the R. aegyptiacus transcriptome. We performed de novo transcriptome assembly using deep RNA sequencing data from 11 distinct tissues from one male and one female bat. We observed high similarity between this transcriptome and those available from other bat species. Gene expression analysis demonstrated clustering of expression profiles by tissue, where we also identified enrichment of tissue-specific gene ontology terms. In addition, we identified and experimentally validated the expression of novel coding transcripts that may be specific to this species. We comprehensively characterized the R. aegyptiacus transcriptome de novo. This transcriptome will be an important resource for understanding bat immunology, physiology, disease pathogenesis, and virus transmission.
Albert K. Lee; Kirsten A. Kulcsar; Oliver Elliott; Hossein Khiabanian; Elyse R. Nagle; Megan E.B. Jones; Brian R. Amman; Mariano Sanchez-Lockhart; Jonathan S. Towner; Gustavo Palacios; Raul Rabadan. De novo transcriptome reconstruction and annotation of the Egyptian rousette bat. BMC Genomics 2015, 16, 1 -11.
AMA StyleAlbert K. Lee, Kirsten A. Kulcsar, Oliver Elliott, Hossein Khiabanian, Elyse R. Nagle, Megan E.B. Jones, Brian R. Amman, Mariano Sanchez-Lockhart, Jonathan S. Towner, Gustavo Palacios, Raul Rabadan. De novo transcriptome reconstruction and annotation of the Egyptian rousette bat. BMC Genomics. 2015; 16 (1):1-11.
Chicago/Turabian StyleAlbert K. Lee; Kirsten A. Kulcsar; Oliver Elliott; Hossein Khiabanian; Elyse R. Nagle; Megan E.B. Jones; Brian R. Amman; Mariano Sanchez-Lockhart; Jonathan S. Towner; Gustavo Palacios; Raul Rabadan. 2015. "De novo transcriptome reconstruction and annotation of the Egyptian rousette bat." BMC Genomics 16, no. 1: 1-11.
Single-molecule real-time (SMRT) sequencing technology with the Pacific Biosciences (PacBio) RS II platform offers the potential to obtain full-length coding regions (∼1100-bp) from MHC class I cDNAs. Despite the relatively high error rate associated with SMRT technology, high quality sequences can be obtained by circular consensus sequencing (CCS) due to the random nature of the error profile. In the present study we first validated the ability of SMRT-CCS to accurately identify class I transcripts in Mauritian-origin cynomolgus macaques (Macaca fascicularis) that have been characterized previously by cloning and Sanger-based sequencing as well as pyrosequencing approaches. We then applied this SMRT-CCS method to characterize 60 novel full-length class I transcript sequences expressed by a cohort of cynomolgus macaques from China. The SMRT-CCS method described here provides a straightforward protocol for characterization of unfragmented single-molecule cDNA transcripts that will potentially revolutionize MHC class I allele discovery in nonhuman primates and other species.
Catherine J. Westbrook; Julie A. Karl; Roger W. Wiseman; Suzanne Mate; Galina Koroleva; Karla Garcia; Mariano Sanchez-Lockhart; David O'Connor; Gustavo Palacios. No assembly required: Full-length MHC class I allele discovery by PacBio circular consensus sequencing. Human Immunology 2015, 76, 891 -896.
AMA StyleCatherine J. Westbrook, Julie A. Karl, Roger W. Wiseman, Suzanne Mate, Galina Koroleva, Karla Garcia, Mariano Sanchez-Lockhart, David O'Connor, Gustavo Palacios. No assembly required: Full-length MHC class I allele discovery by PacBio circular consensus sequencing. Human Immunology. 2015; 76 (12):891-896.
Chicago/Turabian StyleCatherine J. Westbrook; Julie A. Karl; Roger W. Wiseman; Suzanne Mate; Galina Koroleva; Karla Garcia; Mariano Sanchez-Lockhart; David O'Connor; Gustavo Palacios. 2015. "No assembly required: Full-length MHC class I allele discovery by PacBio circular consensus sequencing." Human Immunology 76, no. 12: 891-896.
Summary The 2013–present Western African Ebola virus disease (EVD) outbreak is the largest ever recorded with >28,000 reported cases. Ebola virus (EBOV) genome sequencing has played an important role throughout this outbreak; however, relatively few sequences have been determined from patients in Liberia, the second worst-affected country. Here, we report 140 EBOV genome sequences from the second wave of the Liberian outbreak and analyze them in combination with 782 previously published sequences from throughout the Western African outbreak. While multiple early introductions of EBOV to Liberia are evident, the majority of Liberian EVD cases are consistent with a single introduction, followed by spread and diversification within the country. Movement of the virus within Liberia was widespread, and reintroductions from Liberia served as an important source for the continuation of the already ongoing EVD outbreak in Guinea. Overall, little evidence was found for incremental adaptation of EBOV to the human host.
Jason T. Ladner; Michael Wiley; Suzanne Mate; Gytis Dudas; Karla Prieto; Sean Lovett; Elyse R. Nagle; Brett Beitzel; Merle L. Gilbert; Lawrence Fakoli; Joseph W. Diclaro; Randal Schoepp; Joseph Fair; Jens H. Kuhn; Lisa Hensley; Daniel J. Park; Pardis C. Sabeti; Andrew Rambaut; Mariano Sanchez-Lockhart; Fatorma K. Bolay; Jeffrey R. Kugelman; Gustavo Palacios. Evolution and Spread of Ebola Virus in Liberia, 2014–2015. Cell Host & Microbe 2015, 18, 659 -669.
AMA StyleJason T. Ladner, Michael Wiley, Suzanne Mate, Gytis Dudas, Karla Prieto, Sean Lovett, Elyse R. Nagle, Brett Beitzel, Merle L. Gilbert, Lawrence Fakoli, Joseph W. Diclaro, Randal Schoepp, Joseph Fair, Jens H. Kuhn, Lisa Hensley, Daniel J. Park, Pardis C. Sabeti, Andrew Rambaut, Mariano Sanchez-Lockhart, Fatorma K. Bolay, Jeffrey R. Kugelman, Gustavo Palacios. Evolution and Spread of Ebola Virus in Liberia, 2014–2015. Cell Host & Microbe. 2015; 18 (6):659-669.
Chicago/Turabian StyleJason T. Ladner; Michael Wiley; Suzanne Mate; Gytis Dudas; Karla Prieto; Sean Lovett; Elyse R. Nagle; Brett Beitzel; Merle L. Gilbert; Lawrence Fakoli; Joseph W. Diclaro; Randal Schoepp; Joseph Fair; Jens H. Kuhn; Lisa Hensley; Daniel J. Park; Pardis C. Sabeti; Andrew Rambaut; Mariano Sanchez-Lockhart; Fatorma K. Bolay; Jeffrey R. Kugelman; Gustavo Palacios. 2015. "Evolution and Spread of Ebola Virus in Liberia, 2014–2015." Cell Host & Microbe 18, no. 6: 659-669.