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Simian hemorrhagic fever virus (SHFV) causes acute, lethal disease in macaques. We developed a single-plasmid cDNA-launch infectious clone of SHFV (rSHFV) and modified the clone to rescue an enhanced green fluorescent protein-expressing rSHFV-eGFP that can be used for rapid and quantitative detection of infection. SHFV has a narrow cell tropism in vitro, with only the grivet MA-104 cell line and a few other grivet cell lines being susceptible to virion entry and permissive to infection. Using rSHFV-eGFP, we demonstrate that one cricetid rodent cell line and three ape cell lines also fully support SHFV replication, whereas 55 human cell lines, 11 bat cell lines, and three rodent cells do not. Interestingly, some human and other mammalian cell lines apparently resistant to SHFV infection are permissive after transfection with the rSHFV-eGFP cDNA-launch plasmid. To further demonstrate the investigative potential of the infectious clone system, we introduced stop codons into eight viral open reading frames (ORFs). This approach suggested that at least one ORF, ORF 2b’, is dispensable for SHFV in vitro replication. Our proof-of-principle experiments indicated that rSHFV-eGFP is a useful tool for illuminating the understudied molecular biology of SHFV.
Yingyun Cai; Shuiqing Yu; Ying Fang; Laura Bollinger; Yanhua Li; Michael Lauck; Elena Postnikova; Steven Mazur; Reed Johnson; Courtney Finch; Sheli Radoshitzky; Gustavo Palacios; Thomas Friedrich; Tony Goldberg; David O’Connor; Peter Jahrling; Jens Kuhn. Development and Characterization of a cDNA-Launch Recombinant Simian Hemorrhagic Fever Virus Expressing Enhanced Green Fluorescent Protein: ORF 2b’ Is Not Required for In Vitro Virus Replication. Viruses 2021, 13, 632 .
AMA StyleYingyun Cai, Shuiqing Yu, Ying Fang, Laura Bollinger, Yanhua Li, Michael Lauck, Elena Postnikova, Steven Mazur, Reed Johnson, Courtney Finch, Sheli Radoshitzky, Gustavo Palacios, Thomas Friedrich, Tony Goldberg, David O’Connor, Peter Jahrling, Jens Kuhn. Development and Characterization of a cDNA-Launch Recombinant Simian Hemorrhagic Fever Virus Expressing Enhanced Green Fluorescent Protein: ORF 2b’ Is Not Required for In Vitro Virus Replication. Viruses. 2021; 13 (4):632.
Chicago/Turabian StyleYingyun Cai; Shuiqing Yu; Ying Fang; Laura Bollinger; Yanhua Li; Michael Lauck; Elena Postnikova; Steven Mazur; Reed Johnson; Courtney Finch; Sheli Radoshitzky; Gustavo Palacios; Thomas Friedrich; Tony Goldberg; David O’Connor; Peter Jahrling; Jens Kuhn. 2021. "Development and Characterization of a cDNA-Launch Recombinant Simian Hemorrhagic Fever Virus Expressing Enhanced Green Fluorescent Protein: ORF 2b’ Is Not Required for In Vitro Virus Replication." Viruses 13, no. 4: 632.
Outbreaks of Ebola ebolavirus (EBOV) have been associated with high morbidity and mortality. Milestones have been reached recently in the management of EBOV disease (EVD) with licensure of an EBOV vaccine and two monoclonal antibody therapies. However, neither vaccines nor therapies are available for other disease-causing filoviruses. In preparation for such outbreaks, and for more facile and cost-effective management of EVD, we seek a cocktail containing orally available and room temperature stable drugs with strong activity against multiple filoviruses. We previously showed that (bepridil + sertraline) and (sertraline + toremifene) synergistically suppress EBOV in cell cultures. Here, we describe steps towards testing these combinations in a mouse model of EVD. We identified a vehicle suitable for oral delivery of the component drugs and determined that, thus formulated the drugs are equally active against EBOV as preparations in DMSO, and they maintain activity upon storage in solution for up to seven days. Pharmacokinetic (PK) studies indicated that the drugs in the oral delivery vehicle are well tolerated in mice at the highest doses tested. Collectively the data support advancement of these combinations to tests for synergy in a mouse model of EVD. Moreover, mathematical modeling based on human oral PK projects that the combinations would be more active in humans than their component single drugs.
Courtney Finch; Julie Dyall; Shuang Xu; Elizabeth Nelson; Elena Postnikova; Janie Liang; Huanying Zhou; Lisa DeWald; Craig Thomas; Amy Wang; Xin Xu; Emma Hughes; Patrick Morris; Jon Mirsalis; Linh Nguyen; Maria Arolfo; Bryan Koci; Michael Holbrook; Lisa Hensley; Peter Jahrling; Connie Schmaljohn; Lisa Johansen; Gene Olinger; Joshua Schiffer; Judith White. Formulation, Stability, Pharmacokinetic, and Modeling Studies for Tests of Synergistic Combinations of Orally Available Approved Drugs against Ebola Virus In Vivo. Microorganisms 2021, 9, 566 .
AMA StyleCourtney Finch, Julie Dyall, Shuang Xu, Elizabeth Nelson, Elena Postnikova, Janie Liang, Huanying Zhou, Lisa DeWald, Craig Thomas, Amy Wang, Xin Xu, Emma Hughes, Patrick Morris, Jon Mirsalis, Linh Nguyen, Maria Arolfo, Bryan Koci, Michael Holbrook, Lisa Hensley, Peter Jahrling, Connie Schmaljohn, Lisa Johansen, Gene Olinger, Joshua Schiffer, Judith White. Formulation, Stability, Pharmacokinetic, and Modeling Studies for Tests of Synergistic Combinations of Orally Available Approved Drugs against Ebola Virus In Vivo. Microorganisms. 2021; 9 (3):566.
Chicago/Turabian StyleCourtney Finch; Julie Dyall; Shuang Xu; Elizabeth Nelson; Elena Postnikova; Janie Liang; Huanying Zhou; Lisa DeWald; Craig Thomas; Amy Wang; Xin Xu; Emma Hughes; Patrick Morris; Jon Mirsalis; Linh Nguyen; Maria Arolfo; Bryan Koci; Michael Holbrook; Lisa Hensley; Peter Jahrling; Connie Schmaljohn; Lisa Johansen; Gene Olinger; Joshua Schiffer; Judith White. 2021. "Formulation, Stability, Pharmacokinetic, and Modeling Studies for Tests of Synergistic Combinations of Orally Available Approved Drugs against Ebola Virus In Vivo." Microorganisms 9, no. 3: 566.
We report the discovery and sequence-based molecular characterization of a novel virus, lanama virus (LNMV), in blood samples obtained from two wild vervet monkeys (Chlorocebus pygerythrus), sampled near Lake Nabugabo, Masaka District, Uganda. Sequencing of the complete viral genomes and subsequent phylogenetic analysis identified LNMV as a distinct member of species Kunsagivirus C, in the undercharacterized picornavirid genus Kunsagivirus.
Jens Kuhn; Samuel Sibley; Colin Chapman; Nick Knowles; Michael Lauck; Joshua Johnson; Cristine Lawson; Matthew Lackemeyer; Kim Valenta; Patrick Omeja; Peter Jahrling; David O’Connor; Tony Goldberg. Discovery of Lanama Virus, a Distinct Member of Species Kunsagivirus C (Picornavirales: Picornaviridae), in Wild Vervet Monkeys (Chlorocebus pygerythrus). Viruses 2020, 12, 1436 .
AMA StyleJens Kuhn, Samuel Sibley, Colin Chapman, Nick Knowles, Michael Lauck, Joshua Johnson, Cristine Lawson, Matthew Lackemeyer, Kim Valenta, Patrick Omeja, Peter Jahrling, David O’Connor, Tony Goldberg. Discovery of Lanama Virus, a Distinct Member of Species Kunsagivirus C (Picornavirales: Picornaviridae), in Wild Vervet Monkeys (Chlorocebus pygerythrus). Viruses. 2020; 12 (12):1436.
Chicago/Turabian StyleJens Kuhn; Samuel Sibley; Colin Chapman; Nick Knowles; Michael Lauck; Joshua Johnson; Cristine Lawson; Matthew Lackemeyer; Kim Valenta; Patrick Omeja; Peter Jahrling; David O’Connor; Tony Goldberg. 2020. "Discovery of Lanama Virus, a Distinct Member of Species Kunsagivirus C (Picornavirales: Picornaviridae), in Wild Vervet Monkeys (Chlorocebus pygerythrus)." Viruses 12, no. 12: 1436.
Over the last 15 years, advances in immunofluorescence-imaging based cycling methods, antibody conjugation methods, and automated image processing have facilitated the development of a high-resolution, multiplexed tissue immunofluorescence (MxIF) method with single cell-level quantitation termed Cell DIVETM. Originally developed for fixed oncology samples, here it was evaluated in highly fixed (up to 30 days), archived monkeypox virus-induced inflammatory skin lesions from a retrospective study in 11 rhesus monkeys to determine whether MxIF was comparable to manual H-scoring of chromogenic stains. Six protein markers related to immune and cellular response (CD68, CD3, Hsp70, Hsp90, ERK1/2, ERK1/2 pT202_pY204) were manually quantified (H-scores) by a pathologist from chromogenic IHC double stains on serial sections and compared to MxIF automated single cell quantification of the same markers that were multiplexed on a single tissue section. Overall, there was directional consistency between the H-score and the MxIF results for all markers except phosphorylated ERK1/2 (ERK1/2 pT202_pY204), which showed a decrease in the lesion compared to the adjacent non-lesioned skin by MxIF vs an increase via H-score. Improvements to automated segmentation using machine learning and adding additional cell markers for cell viability are future options for improvement. This method could be useful in infectious disease research as it conserves tissue, provides marker colocalization data on thousands of cells, allowing further cell level data mining as well as a reduction in user bias.
Anup Sood; Yunxia Sui; Elizabeth McDonough; Alberto Santamaría-Pang; Yousef Al-Kofahi; Zhengyu Pang; Peter B. Jahrling; Jens H. Kuhn; Fiona Ginty. Comparison of Multiplexed Immunofluorescence Imaging to Chromogenic Immunohistochemistry of Skin Biomarkers in Response to Monkeypox Virus Infection. Viruses 2020, 12, 787 .
AMA StyleAnup Sood, Yunxia Sui, Elizabeth McDonough, Alberto Santamaría-Pang, Yousef Al-Kofahi, Zhengyu Pang, Peter B. Jahrling, Jens H. Kuhn, Fiona Ginty. Comparison of Multiplexed Immunofluorescence Imaging to Chromogenic Immunohistochemistry of Skin Biomarkers in Response to Monkeypox Virus Infection. Viruses. 2020; 12 (8):787.
Chicago/Turabian StyleAnup Sood; Yunxia Sui; Elizabeth McDonough; Alberto Santamaría-Pang; Yousef Al-Kofahi; Zhengyu Pang; Peter B. Jahrling; Jens H. Kuhn; Fiona Ginty. 2020. "Comparison of Multiplexed Immunofluorescence Imaging to Chromogenic Immunohistochemistry of Skin Biomarkers in Response to Monkeypox Virus Infection." Viruses 12, no. 8: 787.
Ongoing Ebola virus disease outbreaks in the Democratic Republic of the Congo follow the largest recorded outbreak in Western Africa (2013–2016). To combat outbreaks, testing of medical countermeasures (therapeutics or vaccines) requires a well-defined, reproducible, animal model. Here we present Ebola virus disease kinetics in 24 Chinese-origin rhesus monkeys exposed intramuscularly to a highly characterized, commercially available Kikwit Ebola virus Filovirus Animal Non-Clinical Group (FANG) stock. Until reaching predetermined clinical disease endpoint criteria, six animals underwent anesthesia for repeated clinical sampling and were compared to six that did not. Groups of three animals were euthanized and necropsied on days 3, 4, 5, and 6 post-exposure, respectively. In addition, three uninfected animals served as controls. Here, we present detailed characterization of clinical and laboratory disease kinetics and complete blood counts, serum chemistries, Ebola virus titers, and disease kinetics for future medical countermeasure (MCM) study design and control data. We measured no statistical difference in hematology, chemistry values, or time to clinical endpoint in animals that were anesthetized for clinical sampling during the acute disease compared to those that were not.
Richard S. Bennett; James Logue; David X. Liu; Rebecca J. Reeder; Krisztina B. Janosko; Donna L. Perry; Timothy K. Cooper; Russell Byrum; Danny Ragland; Marisa St. Claire; Ricky Adams; Tracey L. Burdette; Tyler M. Brady; Kyra Hadley; M. Colin Waters; Rebecca Shim; William Dowling; Jing Qin; Ian Crozier; Peter B. Jahrling; Lisa E. Hensley. Kikwit Ebola Virus Disease Progression in the Rhesus Monkey Animal Model. Viruses 2020, 12, 753 .
AMA StyleRichard S. Bennett, James Logue, David X. Liu, Rebecca J. Reeder, Krisztina B. Janosko, Donna L. Perry, Timothy K. Cooper, Russell Byrum, Danny Ragland, Marisa St. Claire, Ricky Adams, Tracey L. Burdette, Tyler M. Brady, Kyra Hadley, M. Colin Waters, Rebecca Shim, William Dowling, Jing Qin, Ian Crozier, Peter B. Jahrling, Lisa E. Hensley. Kikwit Ebola Virus Disease Progression in the Rhesus Monkey Animal Model. Viruses. 2020; 12 (7):753.
Chicago/Turabian StyleRichard S. Bennett; James Logue; David X. Liu; Rebecca J. Reeder; Krisztina B. Janosko; Donna L. Perry; Timothy K. Cooper; Russell Byrum; Danny Ragland; Marisa St. Claire; Ricky Adams; Tracey L. Burdette; Tyler M. Brady; Kyra Hadley; M. Colin Waters; Rebecca Shim; William Dowling; Jing Qin; Ian Crozier; Peter B. Jahrling; Lisa E. Hensley. 2020. "Kikwit Ebola Virus Disease Progression in the Rhesus Monkey Animal Model." Viruses 12, no. 7: 753.
Introduction: The development of therapeutics and vaccines to combat Risk Group 4 pathogens, which are associated with high case-fatality rates, is a high priority. Post-exposure prophylactic vaccines have the potential to bridge classical therapeutic and vaccine applications, but little progress has been reported to date. Areas covered: This review provides an overview of post-exposure prophylactic vaccine candidates against Risk Group 4 pathogens. Expert opinion: A few candidate post-exposure prophylactic vaccines protect experimental animals infected with a few Risk Group 4 pathogens, such as filoviruses or hantaviruses, but efficacy of candidate vaccines has not been similarly reported for most other high-consequence pathogens. A major drawback for the further development of existing candidates is the lack of understanding of their mechanisms of action, knowledge of which could help to identify focused paths forward in vaccine development and licensure. These drawbacks to further development ultimately slow progress toward post-exposure prophylactic vaccine licensure.
James Logue; Ian Crozier; Peter B Jahrling; Jens H Kuhn. Post-exposure prophylactic vaccine candidates for the treatment of human Risk Group 4 pathogen infections. Expert Review of Vaccines 2020, 19, 85 -103.
AMA StyleJames Logue, Ian Crozier, Peter B Jahrling, Jens H Kuhn. Post-exposure prophylactic vaccine candidates for the treatment of human Risk Group 4 pathogen infections. Expert Review of Vaccines. 2020; 19 (1):85-103.
Chicago/Turabian StyleJames Logue; Ian Crozier; Peter B Jahrling; Jens H Kuhn. 2020. "Post-exposure prophylactic vaccine candidates for the treatment of human Risk Group 4 pathogen infections." Expert Review of Vaccines 19, no. 1: 85-103.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Timothy K. Cooper; Louis Huzella; Joshua C. Johnson; Oscar Rojas; Sri Yellayi; Mei G. Sun; Sina Bavari; Amanda Bonilla; Randy Hart; Peter B. Jahrling; Jens H. Kuhn; Xiankun Zeng. Author Correction: Histology, immunohistochemistry, and in situ hybridization reveal overlooked Ebola virus target tissues in the Ebola virus disease guinea pig model. Scientific Reports 2019, 9, 1 -1.
AMA StyleTimothy K. Cooper, Louis Huzella, Joshua C. Johnson, Oscar Rojas, Sri Yellayi, Mei G. Sun, Sina Bavari, Amanda Bonilla, Randy Hart, Peter B. Jahrling, Jens H. Kuhn, Xiankun Zeng. Author Correction: Histology, immunohistochemistry, and in situ hybridization reveal overlooked Ebola virus target tissues in the Ebola virus disease guinea pig model. Scientific Reports. 2019; 9 (1):1-1.
Chicago/Turabian StyleTimothy K. Cooper; Louis Huzella; Joshua C. Johnson; Oscar Rojas; Sri Yellayi; Mei G. Sun; Sina Bavari; Amanda Bonilla; Randy Hart; Peter B. Jahrling; Jens H. Kuhn; Xiankun Zeng. 2019. "Author Correction: Histology, immunohistochemistry, and in situ hybridization reveal overlooked Ebola virus target tissues in the Ebola virus disease guinea pig model." Scientific Reports 9, no. 1: 1-1.
Following the largest Ebola virus disease outbreak from 2013 to 2016, viral RNA has been detected in survivors from semen and breast milk long after disease recovery. However, as there have been few cases of sexual transmission, it is unclear whether every RNA positive fluid sample contains infectious virus. Virus isolation, typically using cell culture or animal models, can serve as a tool to determine the infectivity of patient samples. However, the sensitivity of these methods has not been assessed for the Ebola virus isolate, Makona. Described here is an efficiency comparison of Ebola virus Makona isolation using Vero E6, Huh-7, monocyte-derived macrophage cells, and suckling laboratory mice. Isolation sensitivity was similar in all methods tested. Laboratory mice and Huh-7 cells were less affected by toxicity from breast milk than Vero E6 and MDM cells. However, the advantages associated with isolation in Huh-7 cells over laboratory mice, including cost effectiveness, sample volume preservation, and a reduction in animal use, make Huh-7 cells the preferred substrate tested for Ebola virus Makona isolation.
James Logue; Walter Vargas Licona; Timothy K. Cooper; Becky Reeder; Russel Byrum; Jing Qin; Nicole Deiuliis Murphy; Yu Cong; Amanda Bonilla; Jennifer Sword; Wade Weaver; Gregory Kocher; Gene G. Olinger; Peter B. Jahrling; Lisa E. Hensley; Richard S. Bennett. Ebola Virus Isolation Using Huh-7 Cells has Methodological Advantages and Similar Sensitivity to Isolation Using Other Cell Types and Suckling BALB/c Laboratory Mice. Viruses 2019, 11, 161 .
AMA StyleJames Logue, Walter Vargas Licona, Timothy K. Cooper, Becky Reeder, Russel Byrum, Jing Qin, Nicole Deiuliis Murphy, Yu Cong, Amanda Bonilla, Jennifer Sword, Wade Weaver, Gregory Kocher, Gene G. Olinger, Peter B. Jahrling, Lisa E. Hensley, Richard S. Bennett. Ebola Virus Isolation Using Huh-7 Cells has Methodological Advantages and Similar Sensitivity to Isolation Using Other Cell Types and Suckling BALB/c Laboratory Mice. Viruses. 2019; 11 (2):161.
Chicago/Turabian StyleJames Logue; Walter Vargas Licona; Timothy K. Cooper; Becky Reeder; Russel Byrum; Jing Qin; Nicole Deiuliis Murphy; Yu Cong; Amanda Bonilla; Jennifer Sword; Wade Weaver; Gregory Kocher; Gene G. Olinger; Peter B. Jahrling; Lisa E. Hensley; Richard S. Bennett. 2019. "Ebola Virus Isolation Using Huh-7 Cells has Methodological Advantages and Similar Sensitivity to Isolation Using Other Cell Types and Suckling BALB/c Laboratory Mice." Viruses 11, no. 2: 161.
Simian hemorrhagic fever virus (SHFV) causes a fulminant and typically lethal viral hemorrhagic fever (VHF) in macaques (Cercopithecinae: Macaca spp.) but causes subclinical infections in patas monkeys (Cercopithecinae: Erythrocebus patas). This difference in disease course offers a unique opportunity to compare host responses to infection by a VHF-causing virus in biologically similar susceptible and refractory animals. Patas and rhesus monkeys were inoculated side-by-side with SHFV. Unlike the severe disease observed in rhesus monkeys, patas monkeys developed a limited clinical disease characterized by changes in complete blood counts, serum chemistries, and development of lymphadenopathy. Viral RNA was measurable in circulating blood 2 days after exposure, and its duration varied by species. Infectious virus was detected in terminal tissues of both patas and rhesus monkeys. Varying degrees of overlap in changes in serum concentrations of interferon (IFN)-γ, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-6 were observed between patas and rhesus monkeys, suggesting the presence of common and species-specific cytokine responses to infection. Similarly, quantitative immunohistochemistry of livers from terminal monkeys and whole blood flow cytometry revealed varying degrees of overlap in changes in macrophages, natural killer cells, and T-cells. The unexpected degree of overlap in host response suggests that relatively small subsets of a host’s response to infection may be responsible for driving hemorrhagic fever pathogenesis. Furthermore, comparative SHFV infection in patas and rhesus monkeys offers an experimental model to characterize host–response mechanisms associated with viral hemorrhagic fever and evaluate pan-viral hemorrhagic fever countermeasures.
Joseph P. Cornish; Ian N. Moore; Donna L. Perry; Abigail Lara; Mahnaz Minai; Dominique Promeneur; Katie R. Hagen; Kimmo Virtaneva; Monica Paneru; Connor R. Buechler; David H. O’Connor; Adam L. Bailey; Kurt Cooper; Steven Mazur; John G. Bernbaum; James Pettitt; Peter B. Jahrling; Jens H. Kuhn; Reed F. Johnson. Clinical Characterization of Host Response to Simian Hemorrhagic Fever Virus Infection in Permissive and Refractory Hosts: A Model for Determining Mechanisms of VHF Pathogenesis. Viruses 2019, 11, 67 .
AMA StyleJoseph P. Cornish, Ian N. Moore, Donna L. Perry, Abigail Lara, Mahnaz Minai, Dominique Promeneur, Katie R. Hagen, Kimmo Virtaneva, Monica Paneru, Connor R. Buechler, David H. O’Connor, Adam L. Bailey, Kurt Cooper, Steven Mazur, John G. Bernbaum, James Pettitt, Peter B. Jahrling, Jens H. Kuhn, Reed F. Johnson. Clinical Characterization of Host Response to Simian Hemorrhagic Fever Virus Infection in Permissive and Refractory Hosts: A Model for Determining Mechanisms of VHF Pathogenesis. Viruses. 2019; 11 (1):67.
Chicago/Turabian StyleJoseph P. Cornish; Ian N. Moore; Donna L. Perry; Abigail Lara; Mahnaz Minai; Dominique Promeneur; Katie R. Hagen; Kimmo Virtaneva; Monica Paneru; Connor R. Buechler; David H. O’Connor; Adam L. Bailey; Kurt Cooper; Steven Mazur; John G. Bernbaum; James Pettitt; Peter B. Jahrling; Jens H. Kuhn; Reed F. Johnson. 2019. "Clinical Characterization of Host Response to Simian Hemorrhagic Fever Virus Infection in Permissive and Refractory Hosts: A Model for Determining Mechanisms of VHF Pathogenesis." Viruses 11, no. 1: 67.
Lassa fever (LF) survivors develop various clinical manifestations including polyserositis, myalgia, epididymitis, and hearing loss weeks to months after recovery from acute infection. We demonstrate a systemic lymphoplasmacytic and histiocytic arteritis and periarteritis in guinea pigs more than 2 months after recovery from acute Lassa virus (LASV) infection. LASV was detected in the arterial tunica media smooth muscle cells by immunohistochemistry, in situ hybridization, and transmission electron microscopy. Our results suggest that the sequelae of LASV infection may be due to virus persistence resulting in systemic vascular damage. These findings shed light on the pathogenesis of LASV sequelae in convalescent human survivors.
David X Liu; Donna L Perry; Lisa Evans Dewald; Yingyun Cai; Katie R Hagen; Timothy K Cooper; Louis M Huzella; Randy Hart; Amanda Bonilla; John G Bernbaum; Krisztina B Janosko; Ricky Adams; Reed F Johnson; Jens H Kuhn; Matthias Schnell; Ian Crozier; Peter B Jahrling; Juan C De La Torre. Persistence of Lassa Virus Associated With Severe Systemic Arteritis in Convalescing Guinea Pigs (Cavia porcellus). Journal of Infectious Diseases 2018, 219, 1818 -1822.
AMA StyleDavid X Liu, Donna L Perry, Lisa Evans Dewald, Yingyun Cai, Katie R Hagen, Timothy K Cooper, Louis M Huzella, Randy Hart, Amanda Bonilla, John G Bernbaum, Krisztina B Janosko, Ricky Adams, Reed F Johnson, Jens H Kuhn, Matthias Schnell, Ian Crozier, Peter B Jahrling, Juan C De La Torre. Persistence of Lassa Virus Associated With Severe Systemic Arteritis in Convalescing Guinea Pigs (Cavia porcellus). Journal of Infectious Diseases. 2018; 219 (11):1818-1822.
Chicago/Turabian StyleDavid X Liu; Donna L Perry; Lisa Evans Dewald; Yingyun Cai; Katie R Hagen; Timothy K Cooper; Louis M Huzella; Randy Hart; Amanda Bonilla; John G Bernbaum; Krisztina B Janosko; Ricky Adams; Reed F Johnson; Jens H Kuhn; Matthias Schnell; Ian Crozier; Peter B Jahrling; Juan C De La Torre. 2018. "Persistence of Lassa Virus Associated With Severe Systemic Arteritis in Convalescing Guinea Pigs (Cavia porcellus)." Journal of Infectious Diseases 219, no. 11: 1818-1822.
Lassa virus (LASV), a mammarenavirus, infects an estimated 100,000–300,000 individuals yearly in western Africa and frequently causes lethal disease. Currently, no LASV-specific antivirals or vaccines are commercially available for prevention or treatment of Lassa fever, the disease caused by LASV. The development of medical countermeasure screening platforms is a crucial step to yield licensable products. Using reverse genetics, we generated a recombinant wild-type LASV (rLASV-WT) and a modified version thereof encoding a cleavable green fluorescent protein (GFP) as a reporter for rapid and quantitative detection of infection (rLASV-GFP). Both rLASV-WT and wild-type LASV exhibited similar growth kinetics in cultured cells, whereas growth of rLASV-GFP was slightly impaired. GFP reporter expression by rLASV-GFP remained stable over several serial passages in Vero cells. Using two well-characterized broad-spectrum antivirals known to inhibit LASV infection, favipiravir and ribavirin, we demonstrate that rLASV-GFP is a suitable screening tool for the identification of LASV infection inhibitors. Building on these findings, we established a rLASV-GFP-based high-throughput drug discovery screen and an rLASV-GFP-based antibody neutralization assay. Both platforms, now available as a standard tool at the IRF-Frederick (an international resource), will accelerate anti-LASV medical countermeasure discovery and reduce costs of antiviral screens in maximum containment laboratories.
Yíngyún Caì; Masaharu Iwasaki; Brett F. Beitzel; Shuīqìng Yú; Elena N. Postnikova; Beatrice Cubitt; Lisa Evans Dewald; Sheli R. Radoshitzky; Laura Bollinger; Peter B. Jahrling; Gustavo F. Palacios; Juan C. De La Torre; Jens H. Kuhn. Recombinant Lassa Virus Expressing Green Fluorescent Protein as a Tool for High-Throughput Drug Screens and Neutralizing Antibody Assays. Viruses 2018, 10, 655 .
AMA StyleYíngyún Caì, Masaharu Iwasaki, Brett F. Beitzel, Shuīqìng Yú, Elena N. Postnikova, Beatrice Cubitt, Lisa Evans Dewald, Sheli R. Radoshitzky, Laura Bollinger, Peter B. Jahrling, Gustavo F. Palacios, Juan C. De La Torre, Jens H. Kuhn. Recombinant Lassa Virus Expressing Green Fluorescent Protein as a Tool for High-Throughput Drug Screens and Neutralizing Antibody Assays. Viruses. 2018; 10 (11):655.
Chicago/Turabian StyleYíngyún Caì; Masaharu Iwasaki; Brett F. Beitzel; Shuīqìng Yú; Elena N. Postnikova; Beatrice Cubitt; Lisa Evans Dewald; Sheli R. Radoshitzky; Laura Bollinger; Peter B. Jahrling; Gustavo F. Palacios; Juan C. De La Torre; Jens H. Kuhn. 2018. "Recombinant Lassa Virus Expressing Green Fluorescent Protein as a Tool for High-Throughput Drug Screens and Neutralizing Antibody Assays." Viruses 10, no. 11: 655.
Simian hemorrhagic fever virus (SHFV) causes a fulminant and typically lethal viral hemorrhagic fever (VHF) in macaques (Cercopithecinae: Macaca spp.) but causes subclinical infections in patas monkeys (Cercopithecinae: Erythrocebus patas). This difference in disease course offers a unique opportunity to compare host-responses to infection by a VHF-causing virus in biologically similar susceptible and refractory animals. Patas and rhesus monkeys were inoculated side-by-side with SHFV. In contrast to the severe disease observed in rhesus monkeys, patas monkeys developed a limited clinical disease characterized by changes in complete blood counts, serum chemistries, and development of lymphadenopathy. Viremia was measurable 2 days after exposure and its duration varied by species. Infectious virus was detected in terminal tissues of both patas and rhesus monkeys. Varying degrees of overlap in changes in serum concentrations of IFN-γ, MCP-1, and IL-6 were observed between patas and rhesus monkeys, suggesting the presence of common and species-specific cytokine responses to infection. Similarly, quantitative immunohistochemistry of terminal livers and whole blood flow cytometry revealed varying degrees of overlap in changes in macrophages, natural killer cells, and T-cells. The unexpected degree of overlap in host-response suggests that relatively small subsets of a host’s response to infection may be responsible for driving pathogenesis that results in a hemorrhagic fever. Furthermore, comparative SHFV infection in patas and rhesus monkeys offers an experimental model to characterize host-response mechanisms associated with viral hemorrhagic fever and evaluate pan-viral hemorrhagic fever countermeasures.IMPORTANCEHost-response mechanisms involved in pathogenesis of VHFs remain poorly understood. An underlying challenge is separating beneficial, inconsequential, and detrimental host-responses during infection. The comparison of host-responses to infection with the same virus in biologically similar animals that have drastically different disease manifestations allows for the identification of pathogenic mechanisms. SHFV, a surrogate virus for human VHF-causing viruses likely causes subclinical infection in African monkeys such as patas monkeys but can cause severe disease in Asian macaque monkeys. Data from the accompanying article by Buechler et al. support that infection of macaques and baboons with non-SHFV simarteviruses can establish persistent or long-term subclinical infections. Baboons, macaques, and patas monkeys are relatively closely taxonomically related (Cercopithecidae: Cercopithecinae) and therefore offer a unique opportunity to dissect how host-response differences determine disease outcome in VHFs.
Joseph P. Cornish; Ian N. Moore; Donna L. Perry; Abigail Lara; Mahnaz Minai; Dominique Promeneur; Katie R. Hagen; Kimmo Virtaneva; Monica Paneru; Connor Buechler; David H. O’Connor; Adam L. Bailey; Kurt Cooper; Steven Mazur; John G. Bernbaum; James Pettitt; Peter B. Jahrling; Jens H. Kuhn; Reed F. Johnson; Katie R Hagan. Clinical Characterization of Host Response to Simian Hemorrhagic Fever Virus Infection in Permissive and Refractory Hosts: A Model for Determining Mechanisms of VHF Pathogenesis. 2018, 454462 .
AMA StyleJoseph P. Cornish, Ian N. Moore, Donna L. Perry, Abigail Lara, Mahnaz Minai, Dominique Promeneur, Katie R. Hagen, Kimmo Virtaneva, Monica Paneru, Connor Buechler, David H. O’Connor, Adam L. Bailey, Kurt Cooper, Steven Mazur, John G. Bernbaum, James Pettitt, Peter B. Jahrling, Jens H. Kuhn, Reed F. Johnson, Katie R Hagan. Clinical Characterization of Host Response to Simian Hemorrhagic Fever Virus Infection in Permissive and Refractory Hosts: A Model for Determining Mechanisms of VHF Pathogenesis. . 2018; ():454462.
Chicago/Turabian StyleJoseph P. Cornish; Ian N. Moore; Donna L. Perry; Abigail Lara; Mahnaz Minai; Dominique Promeneur; Katie R. Hagen; Kimmo Virtaneva; Monica Paneru; Connor Buechler; David H. O’Connor; Adam L. Bailey; Kurt Cooper; Steven Mazur; John G. Bernbaum; James Pettitt; Peter B. Jahrling; Jens H. Kuhn; Reed F. Johnson; Katie R Hagan. 2018. "Clinical Characterization of Host Response to Simian Hemorrhagic Fever Virus Infection in Permissive and Refractory Hosts: A Model for Determining Mechanisms of VHF Pathogenesis." , no. : 454462.
Currently, no FDA-approved vaccines or treatments are available for Ebola virus disease (EVD), and therapy remains largely supportive. Ebola virus (EBOV) has broad tissue tropism and can infect a variety of cells including epithelial cells. Epithelial cells differ from most other cell types by their polarized phenotype and barrier function. In polarized cells, the apical and basolateral membrane domains are demarcated by tight junctions, and specialized sorting machinery, which results in a difference in composition between the two membrane domains. These specialized sorting functions can have important consequences for viral infections. Differential localization of a viral receptor can restrict virus entry to a particular membrane while polarized sorting can lead to a vectorial virus release. The present study investigated the impact of cell polarity on EBOV infection. Characteristics of EBOV infection in polarized cells were evaluated in the polarized Caco-2 model grown on semipermeable transwells. Transepithelial resistance (TEER), which is a function of tight junctions, was used to assess epithelial cell polarization. EBOV infection was assessed with immunofluorescence microscopy and qPCR. Statistical significance was calculated using one-way ANOVA and significance was set at p < 0.05. Our data indicate that EBOV preferentially infects cells from the basolateral route, and this preference may be influenced by the resistance across the Caco-2 monolayer. Infection occurs without changes in cellular permeability. Further, our data show that basolateral infection bias may be dependent on polarized distribution of heparan sulfate, a known viral attachment factor. Treatment with iota-carrageenan, or heparin lyase, which interrupts viral interaction with cellular heparan sulfate, significantly reduced cell susceptibility to basolateral infection, likely by inhibiting virus attachment. Our results show cell polarity has an impact on EBOV infection. EBOV preferentially infects polarized cells through the basolateral route. Access to heparan sulfate is an important factor during basolateral infection and blocking interaction of cellular heparan sulfate with virus leads to significant inhibition of basolateral infection in the polarized Caco-2 cell model.
Manasi Tamhankar; Dawn M. Gerhardt; Richard S. Bennett; Nicole Murphy; Peter B. Jahrling; Jean L. Patterson. Heparan sulfate is an important mediator of Ebola virus infection in polarized epithelial cells. Virology Journal 2018, 15, 1 -12.
AMA StyleManasi Tamhankar, Dawn M. Gerhardt, Richard S. Bennett, Nicole Murphy, Peter B. Jahrling, Jean L. Patterson. Heparan sulfate is an important mediator of Ebola virus infection in polarized epithelial cells. Virology Journal. 2018; 15 (1):1-12.
Chicago/Turabian StyleManasi Tamhankar; Dawn M. Gerhardt; Richard S. Bennett; Nicole Murphy; Peter B. Jahrling; Jean L. Patterson. 2018. "Heparan sulfate is an important mediator of Ebola virus infection in polarized epithelial cells." Virology Journal 15, no. 1: 1-12.
Timothy K Cooper; Jennifer Sword; Joshua C Johnson; Amanda Bonilla; Randy Hart; David X Liu; John G Bernbaum; Kurt Cooper; Peter B Jahrling; Lisa E Hensley. New Insights Into Marburg Virus Disease Pathogenesis in the Rhesus Macaque Model. The Journal of Infectious Diseases 2018, 1 .
AMA StyleTimothy K Cooper, Jennifer Sword, Joshua C Johnson, Amanda Bonilla, Randy Hart, David X Liu, John G Bernbaum, Kurt Cooper, Peter B Jahrling, Lisa E Hensley. New Insights Into Marburg Virus Disease Pathogenesis in the Rhesus Macaque Model. The Journal of Infectious Diseases. 2018; ():1.
Chicago/Turabian StyleTimothy K Cooper; Jennifer Sword; Joshua C Johnson; Amanda Bonilla; Randy Hart; David X Liu; John G Bernbaum; Kurt Cooper; Peter B Jahrling; Lisa E Hensley. 2018. "New Insights Into Marburg Virus Disease Pathogenesis in the Rhesus Macaque Model." The Journal of Infectious Diseases , no. : 1.
At the onset of the 2013–2016 epidemic of Ebola virus disease (EVD), no vaccine or antiviral medication was approved for treatment. Therefore, considerable efforts were directed towards the concept of drug repurposing or repositioning. Amiodarone, an approved multi-ion channel blocker for the treatment of cardiac arrhythmia, was reported to inhibit filovirus entry in vitro. Compassionate use of amiodarone in EVD patients indicated a possible survival benefit. In support of further clinical testing, we confirmed anti-Ebola virus activity of amiodarone in different cell types. Despite promising in vitro results, amiodarone failed to protect guinea pigs from a lethal dose of Ebola virus.
Julie Dyall; Joshua C Johnson; Brit J Hart; Elena Postnikova; Yu Cong; Huanying Zhou; Dawn M Gerhardt; Julia Michelotti; Anna Honko; Steven Kern; Lisa Evans Dewald; Kathleen G O’Loughlin; Carol E Green; Jon C Mirsalis; Richard Bennett; Gene Olinger; Peter B Jahrling; Lisa Hensley. In Vitro and In Vivo Activity of Amiodarone Against Ebola Virus. Journal of Infectious Diseases 2018, 218, S592 -S596.
AMA StyleJulie Dyall, Joshua C Johnson, Brit J Hart, Elena Postnikova, Yu Cong, Huanying Zhou, Dawn M Gerhardt, Julia Michelotti, Anna Honko, Steven Kern, Lisa Evans Dewald, Kathleen G O’Loughlin, Carol E Green, Jon C Mirsalis, Richard Bennett, Gene Olinger, Peter B Jahrling, Lisa Hensley. In Vitro and In Vivo Activity of Amiodarone Against Ebola Virus. Journal of Infectious Diseases. 2018; 218 (suppl_5):S592-S596.
Chicago/Turabian StyleJulie Dyall; Joshua C Johnson; Brit J Hart; Elena Postnikova; Yu Cong; Huanying Zhou; Dawn M Gerhardt; Julia Michelotti; Anna Honko; Steven Kern; Lisa Evans Dewald; Kathleen G O’Loughlin; Carol E Green; Jon C Mirsalis; Richard Bennett; Gene Olinger; Peter B Jahrling; Lisa Hensley. 2018. "In Vitro and In Vivo Activity of Amiodarone Against Ebola Virus." Journal of Infectious Diseases 218, no. suppl_5: S592-S596.
Lisa Evans Dewald; Julie Dyall; Jennifer M Sword; Lisa Torzewski; Huanying Zhou; Elena Postnikova; Erin Kollins; Isis Alexander; Robin Gross; Yu Cong; Dawn M Gerhardt; Reed F Johnson; Gene G Olinger; Michael R Holbrook; Lisa E Hensley; Peter B Jahrling. The Calcium Channel Blocker Bepridil Demonstrates Efficacy in the Murine Model of Marburg Virus Disease. The Journal of Infectious Diseases 2018, 218, S588 -S591.
AMA StyleLisa Evans Dewald, Julie Dyall, Jennifer M Sword, Lisa Torzewski, Huanying Zhou, Elena Postnikova, Erin Kollins, Isis Alexander, Robin Gross, Yu Cong, Dawn M Gerhardt, Reed F Johnson, Gene G Olinger, Michael R Holbrook, Lisa E Hensley, Peter B Jahrling. The Calcium Channel Blocker Bepridil Demonstrates Efficacy in the Murine Model of Marburg Virus Disease. The Journal of Infectious Diseases. 2018; 218 (suppl_5):S588-S591.
Chicago/Turabian StyleLisa Evans Dewald; Julie Dyall; Jennifer M Sword; Lisa Torzewski; Huanying Zhou; Elena Postnikova; Erin Kollins; Isis Alexander; Robin Gross; Yu Cong; Dawn M Gerhardt; Reed F Johnson; Gene G Olinger; Michael R Holbrook; Lisa E Hensley; Peter B Jahrling. 2018. "The Calcium Channel Blocker Bepridil Demonstrates Efficacy in the Murine Model of Marburg Virus Disease." The Journal of Infectious Diseases 218, no. suppl_5: S588-S591.
Ebola virus (EBOV) disease is a viral hemorrhagic fever with a high case-fatality rate in humans. This disease is caused by four members of the filoviral genus Ebolavirus, including EBOV. The natural hosts reservoirs of ebolaviruses remain to be identified. Glycoprotein 2 of reptarenaviruses, known to infect only boa constrictors and pythons, is similar in sequence and structure to ebolaviral glycoprotein 2, suggesting that EBOV may be able to infect reptilian cells. Therefore, we serially passaged EBOV and a distantly related filovirus, Marburg virus (MARV), in boa constrictor JK cells and characterized viral infection/replication and mutational frequency by confocal imaging and sequencing. We observed that EBOV efficiently infected and replicated in JK cells, but MARV did not. In contrast to most cell lines, EBOV-infected JK cells did not result in an obvious cytopathic effect. Surprisingly, genomic characterization of serial-passaged EBOV in JK cells revealed that genomic adaptation was not required for infection. Deep sequencing coverage (>10,000×) demonstrated the existence of only a single nonsynonymous variant (EBOV glycoprotein precursor pre-GP T544I) of unknown significance within the viral population that exhibited a shift in frequency of at least 10 per cent over six serial passages. In summary, we present the first reptilian cell line that replicates a filovirus at high titers, and for the first time demonstrate a filovirus genus-specific restriction to MARV in a cell line. Our data suggest the possibility that there may be differences between the natural host spectra of ebolaviruses and marburgviruses.
Greg Fedewa; Sheli R Radoshitzky; Xiǎolì Chī; Lián Dǒng; Xiankun Zeng; Melissa Spear; Nicolas Strauli; Melinda Ng; Kartik Chandran; Mark D Stenglein; Ryan D Hernandez; Peter B Jahrling; Jens H Kuhn; Joseph L DeRisi. Ebola virus, but not Marburg virus, replicates efficiently and without required adaptation in snake cells. Virus Evolution 2018, 4, vey034 .
AMA StyleGreg Fedewa, Sheli R Radoshitzky, Xiǎolì Chī, Lián Dǒng, Xiankun Zeng, Melissa Spear, Nicolas Strauli, Melinda Ng, Kartik Chandran, Mark D Stenglein, Ryan D Hernandez, Peter B Jahrling, Jens H Kuhn, Joseph L DeRisi. Ebola virus, but not Marburg virus, replicates efficiently and without required adaptation in snake cells. Virus Evolution. 2018; 4 (2):vey034.
Chicago/Turabian StyleGreg Fedewa; Sheli R Radoshitzky; Xiǎolì Chī; Lián Dǒng; Xiankun Zeng; Melissa Spear; Nicolas Strauli; Melinda Ng; Kartik Chandran; Mark D Stenglein; Ryan D Hernandez; Peter B Jahrling; Jens H Kuhn; Joseph L DeRisi. 2018. "Ebola virus, but not Marburg virus, replicates efficiently and without required adaptation in snake cells." Virus Evolution 4, no. 2: vey034.
A need to develop therapeutics to treat Ebola virus disease patients in remote and resource-challenged settings remains in the wake of the 2013–2016 epidemic in West Africa. Toward this goal, we screened drugs under consideration as treatment options and other drugs of interest, most being small molecules approved by the Food and Drug Administration. Drugs demonstrating in vitro antiviral activity were advanced for evaluation in combinations because of advantages often provided by drug cocktails. Drugs were screened for blockade of Ebola virus infection in cultured cells. Twelve drugs were tested in all (78 pair-wise) combinations, and 3 were tested in a subset of combinations. Multiple synergistic drug pairs emerged, with the majority comprising 2 entry inhibitors. For the pairs of entry inhibitors studied, synergy was demonstrated at the level of virus entry into host cells. Highly synergistic pairs included aripiprazole/piperacetazine, sertraline/toremifene, sertraline/bepridil, and amodiaquine/clomiphene. Our study shows the feasibility of identifying pairs of approved drugs that synergistically block Ebola virus infection in cell cultures. We discuss our findings in terms of the theoretic ability of these or alternate combinations to reach therapeutic levels. Future research will assess selected combinations in small-animal models of Ebola virus disease.
Julie Dyall; Elizabeth A Nelson; Lisa Evans DeWald; Rajarshi Guha; Brit J Hart; Huanying Zhou; Elena Postnikova; James Logue; Walter M Vargas; Robin Gross; Julia Michelotti; Nicole Deiuliis; Richard Bennett; Ian Crozier; Michael R Holbrook; Patrick J Morris; Carleen Klumpp-Thomas; Crystal McKnight; Tim Mierzwa; Paul Shinn; Pamela J Glass; Lisa M Johansen; Peter B Jahrling; Lisa E Hensley; Gene Olinger; Craig Thomas; Judith M White. Identification of Combinations of Approved Drugs With Synergistic Activity Against Ebola Virus in Cell Cultures. Journal of Infectious Diseases 2018, 218, S672 -S678.
AMA StyleJulie Dyall, Elizabeth A Nelson, Lisa Evans DeWald, Rajarshi Guha, Brit J Hart, Huanying Zhou, Elena Postnikova, James Logue, Walter M Vargas, Robin Gross, Julia Michelotti, Nicole Deiuliis, Richard Bennett, Ian Crozier, Michael R Holbrook, Patrick J Morris, Carleen Klumpp-Thomas, Crystal McKnight, Tim Mierzwa, Paul Shinn, Pamela J Glass, Lisa M Johansen, Peter B Jahrling, Lisa E Hensley, Gene Olinger, Craig Thomas, Judith M White. Identification of Combinations of Approved Drugs With Synergistic Activity Against Ebola Virus in Cell Cultures. Journal of Infectious Diseases. 2018; 218 (suppl_5):S672-S678.
Chicago/Turabian StyleJulie Dyall; Elizabeth A Nelson; Lisa Evans DeWald; Rajarshi Guha; Brit J Hart; Huanying Zhou; Elena Postnikova; James Logue; Walter M Vargas; Robin Gross; Julia Michelotti; Nicole Deiuliis; Richard Bennett; Ian Crozier; Michael R Holbrook; Patrick J Morris; Carleen Klumpp-Thomas; Crystal McKnight; Tim Mierzwa; Paul Shinn; Pamela J Glass; Lisa M Johansen; Peter B Jahrling; Lisa E Hensley; Gene Olinger; Craig Thomas; Judith M White. 2018. "Identification of Combinations of Approved Drugs With Synergistic Activity Against Ebola Virus in Cell Cultures." Journal of Infectious Diseases 218, no. suppl_5: S672-S678.
Sexual transmission of Ebola virus (EBOV) has been demonstrated more than a year after recovery from the acute phase of Ebola virus disease (EVD). The mechanisms underlying EBOV persistence and sexual transmission are not currently understood. Using the acute macaque model of EVD, we hypothesized EBOV would infect the reproductive tissues and sought to localize the infection in these tissues using immunohistochemistry and transmission electron microscopy. In four female and eight male macaques that succumbed to EVD between 6 and 9 days after EBOV challenge, we demonstrate widespread EBOV infection of the interstitial tissues and endothelium in the ovary, uterus, testis, seminal vesicle, epididymis, and prostate gland, with minimal associated tissue immune response or organ pathology. Given the widespread involvement of EBOV in the reproductive tracts of both male and female macaques, it is reasonable to surmise that our understanding of the mechanisms underlying sexual transmission of EVD and persistence of EBOV in immune-privileged sites would be facilitated by the development of a nonhuman primate model in which the macaques survived past the acute stage into convalescence.
Donna L. Perry; Louis M. Huzella; John G. Bernbaum; Michael R. Holbrook; Peter B. Jahrling; Katie R. Hagen; Matthias J. Schnell; Reed F. Johnson. Ebola Virus Localization in the Macaque Reproductive Tract during Acute Ebola Virus Disease. The American Journal of Pathology 2018, 188, 550 -558.
AMA StyleDonna L. Perry, Louis M. Huzella, John G. Bernbaum, Michael R. Holbrook, Peter B. Jahrling, Katie R. Hagen, Matthias J. Schnell, Reed F. Johnson. Ebola Virus Localization in the Macaque Reproductive Tract during Acute Ebola Virus Disease. The American Journal of Pathology. 2018; 188 (3):550-558.
Chicago/Turabian StyleDonna L. Perry; Louis M. Huzella; John G. Bernbaum; Michael R. Holbrook; Peter B. Jahrling; Katie R. Hagen; Matthias J. Schnell; Reed F. Johnson. 2018. "Ebola Virus Localization in the Macaque Reproductive Tract during Acute Ebola Virus Disease." The American Journal of Pathology 188, no. 3: 550-558.
Survivors of Ebola virus infection may become subclinically infected, but whether animal models recapitulate this complication is unclear. Using histology in combination with immunohistochemistry and in situ hybridization in a retrospective review of a guinea pig confirmation-of-virulence study, we demonstrate for the first time Ebola virus infection in hepatic oval cells, the endocardium and stroma of the atrioventricular valves and chordae tendinae, satellite cells of peripheral ganglia, neurofibroblasts and Schwann cells of peripheral nerves and ganglia, smooth muscle cells of the uterine myometrium and vaginal wall, acini of the parotid salivary glands, thyroid follicular cells, adrenal medullary cells, pancreatic islet cells, endometrial glandular and surface epithelium, and the epithelium of the vagina, penis and, prepuce. These findings indicate that standard animal models for Ebola virus disease are not as well-described as previously thought and may serve as a stepping stone for future identification of potential sites of virus persistence.
Timothy K. Cooper; Louis Huzella; Joshua C. Johnson; Oscar Rojas; Sri Yellayi; Mei G. Sun; Sina Bavari; Amanda Bonilla; Randy Hart; Peter B. Jahrling; Jens H. Kuhn; Xiankun Zeng. Histology, immunohistochemistry, and in situ hybridization reveal overlooked Ebola virus target tissues in the Ebola virus disease guinea pig model. Scientific Reports 2018, 8, 1250 .
AMA StyleTimothy K. Cooper, Louis Huzella, Joshua C. Johnson, Oscar Rojas, Sri Yellayi, Mei G. Sun, Sina Bavari, Amanda Bonilla, Randy Hart, Peter B. Jahrling, Jens H. Kuhn, Xiankun Zeng. Histology, immunohistochemistry, and in situ hybridization reveal overlooked Ebola virus target tissues in the Ebola virus disease guinea pig model. Scientific Reports. 2018; 8 (1):1250.
Chicago/Turabian StyleTimothy K. Cooper; Louis Huzella; Joshua C. Johnson; Oscar Rojas; Sri Yellayi; Mei G. Sun; Sina Bavari; Amanda Bonilla; Randy Hart; Peter B. Jahrling; Jens H. Kuhn; Xiankun Zeng. 2018. "Histology, immunohistochemistry, and in situ hybridization reveal overlooked Ebola virus target tissues in the Ebola virus disease guinea pig model." Scientific Reports 8, no. 1: 1250.