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David H. O’Connor
Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America

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Article
Published: 31 July 2021
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The SARS-CoV-2 Delta variant might cause high viral loads, is highly transmissible, and contains mutations that confer partial immune escape 1,2. Outbreak investigations suggest that vaccinated persons can spread Delta 3,4. We compared RT-PCR cycle threshold (Ct) data from 699 swab specimens collected in Wisconsin 29 June through 31 July 2021 and tested with a qualitative assay by a single contract laboratory. Specimens came from residents of 36 counties, most in southern and southeastern Wisconsin, and 81% of cases were not associated with an outbreak. During this time, estimated prevalence of Delta variants in Wisconsin increased from 69% to over 95%. Vaccination status was determined via self-reporting and state immunization records (Supplemental Figure 1).

ACS Style

Kasen K. Riemersma; Brittany E. Grogan; Amanda Kita-Yarbro; Peter J. Halfmann; Hannah E. Segaloff; Anna Kocharian; Kelsey R. Florek; Ryan Westergaard; Allen Bateman; Gunnar E. Jeppson; Yoshihiro Kawaoka; David H. O’Connor; Thomas C. Friedrich; Katarina M. Grande. Shedding of Infectious SARS-CoV-2 Despite Vaccination. 2021, 1 .

AMA Style

Kasen K. Riemersma, Brittany E. Grogan, Amanda Kita-Yarbro, Peter J. Halfmann, Hannah E. Segaloff, Anna Kocharian, Kelsey R. Florek, Ryan Westergaard, Allen Bateman, Gunnar E. Jeppson, Yoshihiro Kawaoka, David H. O’Connor, Thomas C. Friedrich, Katarina M. Grande. Shedding of Infectious SARS-CoV-2 Despite Vaccination. . 2021; ():1.

Chicago/Turabian Style

Kasen K. Riemersma; Brittany E. Grogan; Amanda Kita-Yarbro; Peter J. Halfmann; Hannah E. Segaloff; Anna Kocharian; Kelsey R. Florek; Ryan Westergaard; Allen Bateman; Gunnar E. Jeppson; Yoshihiro Kawaoka; David H. O’Connor; Thomas C. Friedrich; Katarina M. Grande. 2021. "Shedding of Infectious SARS-CoV-2 Despite Vaccination." , no. : 1.

Research article
Published: 30 July 2021 in PLOS Neglected Tropical Diseases
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Concerns have arisen that pre-existing immunity to dengue virus (DENV) could enhance Zika virus (ZIKV) disease, due to the homology between ZIKV and DENV and the observation of antibody-dependent enhancement (ADE) among DENV serotypes. To date, no study has examined the impact of pre-existing DENV immunity on ZIKV pathogenesis during pregnancy in a translational non-human primate model. Here we show that macaques with a prior DENV-2 exposure had a higher burden of ZIKV vRNA in maternal-fetal interface tissues as compared to DENV-naive macaques. However, pre-existing DENV immunity had no detectable impact on ZIKV replication kinetics in maternal plasma, and all pregnancies progressed to term without adverse outcomes or gross fetal abnormalities detectable at delivery. Understanding the risks of ADE to pregnant women worldwide is critical as vaccines against DENV and ZIKV are developed and licensed and as DENV and ZIKV continue to circulate.

ACS Style

Chelsea M. Crooks; Andrea M. Weiler; Sierra L. Rybarczyk; Mason I. Bliss; Anna S. Jaeger; Megan E. Murphy; Heather A. Simmons; Andres Mejia; Michael K. Fritsch; Jennifer M. Hayes; Jens C. Eickhoff; Ann M. Mitzey; Elaina Razo; Katarina M. Braun; Elizabeth A. Brown; Keisuke Yamamoto; Phoenix M. Shepherd; Amber Possell; Kara Weaver; Kathleen M. Antony; Terry K. Morgan; Christina M. Newman; Dawn M. Dudley; Nancy Schultz-Darken; Eric Peterson; Leah C. Katzelnick; Angel Balmaseda; Eva Harris; David H. O’Connor; Emma L. Mohr; Thaddeus G. Golos; Thomas C. Friedrich; Matthew T. Aliota. Previous exposure to dengue virus is associated with increased Zika virus burden at the maternal-fetal interface in rhesus macaques. PLOS Neglected Tropical Diseases 2021, 15, e0009641 .

AMA Style

Chelsea M. Crooks, Andrea M. Weiler, Sierra L. Rybarczyk, Mason I. Bliss, Anna S. Jaeger, Megan E. Murphy, Heather A. Simmons, Andres Mejia, Michael K. Fritsch, Jennifer M. Hayes, Jens C. Eickhoff, Ann M. Mitzey, Elaina Razo, Katarina M. Braun, Elizabeth A. Brown, Keisuke Yamamoto, Phoenix M. Shepherd, Amber Possell, Kara Weaver, Kathleen M. Antony, Terry K. Morgan, Christina M. Newman, Dawn M. Dudley, Nancy Schultz-Darken, Eric Peterson, Leah C. Katzelnick, Angel Balmaseda, Eva Harris, David H. O’Connor, Emma L. Mohr, Thaddeus G. Golos, Thomas C. Friedrich, Matthew T. Aliota. Previous exposure to dengue virus is associated with increased Zika virus burden at the maternal-fetal interface in rhesus macaques. PLOS Neglected Tropical Diseases. 2021; 15 (7):e0009641.

Chicago/Turabian Style

Chelsea M. Crooks; Andrea M. Weiler; Sierra L. Rybarczyk; Mason I. Bliss; Anna S. Jaeger; Megan E. Murphy; Heather A. Simmons; Andres Mejia; Michael K. Fritsch; Jennifer M. Hayes; Jens C. Eickhoff; Ann M. Mitzey; Elaina Razo; Katarina M. Braun; Elizabeth A. Brown; Keisuke Yamamoto; Phoenix M. Shepherd; Amber Possell; Kara Weaver; Kathleen M. Antony; Terry K. Morgan; Christina M. Newman; Dawn M. Dudley; Nancy Schultz-Darken; Eric Peterson; Leah C. Katzelnick; Angel Balmaseda; Eva Harris; David H. O’Connor; Emma L. Mohr; Thaddeus G. Golos; Thomas C. Friedrich; Matthew T. Aliota. 2021. "Previous exposure to dengue virus is associated with increased Zika virus burden at the maternal-fetal interface in rhesus macaques." PLOS Neglected Tropical Diseases 15, no. 7: e0009641.

Article
Published: 14 July 2021 in Nature Communications
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The COVID-19 pandemic exposed difficulties in scaling current quantitative PCR (qPCR)-based diagnostic methodologies for large-scale infectious disease testing. Bottlenecks include lengthy multi-step processes for nucleic acid extraction followed by qPCR readouts, which require costly instrumentation and infrastructure, as well as reagent and plastic consumable shortages stemming from supply chain constraints. Here we report an Oil Immersed Lossless Total Analysis System (OIL-TAS), which integrates RNA extraction and detection onto a single device that is simple, rapid, cost effective, and requires minimal supplies and infrastructure to perform. We validated the performance of OIL-TAS using contrived SARS-CoV-2 viral particle samples and clinical nasopharyngeal swab samples. OIL-TAS showed a 93% positive predictive agreement (n = 57) and 100% negative predictive agreement (n = 10) with clinical SARS-CoV-2 qPCR assays in testing clinical samples, highlighting its potential to be a faster, cheaper, and easier-to-deploy alternative for infectious disease testing.

ACS Style

Duane S. Juang; Terry D. Juang; Dawn M. Dudley; Christina M. Newman; Molly A. Accola; William M. Rehrauer; Thomas C. Friedrich; David H. O’Connor; David J. Beebe. Oil immersed lossless total analysis system for integrated RNA extraction and detection of SARS-CoV-2. Nature Communications 2021, 12, 1 -9.

AMA Style

Duane S. Juang, Terry D. Juang, Dawn M. Dudley, Christina M. Newman, Molly A. Accola, William M. Rehrauer, Thomas C. Friedrich, David H. O’Connor, David J. Beebe. Oil immersed lossless total analysis system for integrated RNA extraction and detection of SARS-CoV-2. Nature Communications. 2021; 12 (1):1-9.

Chicago/Turabian Style

Duane S. Juang; Terry D. Juang; Dawn M. Dudley; Christina M. Newman; Molly A. Accola; William M. Rehrauer; Thomas C. Friedrich; David H. O’Connor; David J. Beebe. 2021. "Oil immersed lossless total analysis system for integrated RNA extraction and detection of SARS-CoV-2." Nature Communications 12, no. 1: 1-9.

Infectious diseases
Published: 18 June 2021 in PLOS Biology
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The search for potential antibody-based diagnostics, vaccines, and therapeutics for pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused almost exclusively on the spike (S) and nucleocapsid (N) proteins. Coronavirus membrane (M), ORF3a, and ORF8 proteins are humoral immunogens in other coronaviruses (CoVs) but remain largely uninvestigated for SARS-CoV-2. Here, we use ultradense peptide microarray mapping to show that SARS-CoV-2 infection induces robust antibody responses to epitopes throughout the SARS-CoV-2 proteome, particularly in M, in which 1 epitope achieved excellent diagnostic accuracy. We map 79 B cell epitopes throughout the SARS-CoV-2 proteome and demonstrate that antibodies that develop in response to SARS-CoV-2 infection bind homologous peptide sequences in the 6 other known human CoVs. We also confirm reactivity against 4 of our top-ranking epitopes by enzyme-linked immunosorbent assay (ELISA). Illness severity correlated with increased reactivity to 9 SARS-CoV-2 epitopes in S, M, N, and ORF3a in our population. Our results demonstrate previously unknown, highly reactive B cell epitopes throughout the full proteome of SARS-CoV-2 and other CoV proteins.

ACS Style

Anna S. Heffron; Sean J. McIlwain; Maya F. Amjadi; David A. Baker; Saniya Khullar; Tammy Armbrust; Peter J. Halfmann; Yoshihiro Kawaoka; Ajay K. Sethi; Ann C. Palmenberg; Miriam A. Shelef; David H. O’Connor; Irene M. Ong. The landscape of antibody binding in SARS-CoV-2 infection. PLOS Biology 2021, 19, e3001265 .

AMA Style

Anna S. Heffron, Sean J. McIlwain, Maya F. Amjadi, David A. Baker, Saniya Khullar, Tammy Armbrust, Peter J. Halfmann, Yoshihiro Kawaoka, Ajay K. Sethi, Ann C. Palmenberg, Miriam A. Shelef, David H. O’Connor, Irene M. Ong. The landscape of antibody binding in SARS-CoV-2 infection. PLOS Biology. 2021; 19 (6):e3001265.

Chicago/Turabian Style

Anna S. Heffron; Sean J. McIlwain; Maya F. Amjadi; David A. Baker; Saniya Khullar; Tammy Armbrust; Peter J. Halfmann; Yoshihiro Kawaoka; Ajay K. Sethi; Ann C. Palmenberg; Miriam A. Shelef; David H. O’Connor; Irene M. Ong. 2021. "The landscape of antibody binding in SARS-CoV-2 infection." PLOS Biology 19, no. 6: e3001265.

Comparative study
Published: 17 June 2021 in Proceedings of the National Academy of Sciences
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The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a key role in viral infectivity. It is also the major antigen stimulating the host's protective immune response, specifically, the production of neutralizing antibodies. Recently, a new variant of SARS-CoV-2 possessing multiple mutations in the S protein, designated P.1, emerged in Brazil. Here, we characterized a P.1 variant isolated in Japan by using Syrian hamsters, a well-established small animal model for the study of SARS-CoV-2 disease (COVID-19). In hamsters, the variant showed replicative abilities and pathogenicity similar to those of early and contemporary strains (i.e., SARS-CoV-2 bearing aspartic acid [D] or glycine [G] at position 614 of the S protein). Sera and/or plasma from convalescent patients and BNT162b2 messenger RNA vaccinees showed comparable neutralization titers across the P.1 variant, S-614D, and S-614G strains. In contrast, the S-614D and S-614G strains were less well recognized than the P.1 variant by serum from a P.1-infected patient. Prior infection with S-614D or S-614G strains efficiently prevented the replication of the P.1 variant in the lower respiratory tract of hamsters upon reinfection. In addition, passive transfer of neutralizing antibodies to hamsters infected with the P.1 variant or the S-614G strain led to reduced virus replication in the lower respiratory tract. However, the effect was less pronounced against the P.1 variant than the S-614G strain. These findings suggest that the P.1 variant may be somewhat antigenically different from the early and contemporary strains of SARS-CoV-2.

ACS Style

Masaki Imai; Peter J. Halfmann; Seiya Yamayoshi; Kiyoko Iwatsuki-Horimoto; Shiho Chiba; Tokiko Watanabe; Noriko Nakajima; Mutsumi Ito; Makoto Kuroda; Maki Kiso; Tadashi Maemura; Kenta Takahashi; Samantha Loeber; Masato Hatta; Michiko Koga; Hiroyuki Nagai; Shinya Yamamoto; Makoto Saito; Eisuke Adachi; Osamu Akasaka; Morio Nakamura; Ichiro Nakachi; Takayuki Ogura; Rie Baba; Kensuke Fujita; Junichi Ochi; Keiko Mitamura; Hideaki Kato; Hideaki Nakajima; Kazuma Yagi; Shin-Ichiro Hattori; Kenji Maeda; Tetsuya Suzuki; Yusuke Miyazato; Riccardo Valdez; Carmen Gherasim; Yuri Furusawa; Moe Okuda; Michiko Ujie; Tiago J. S. Lopes; Atsuhiro Yasuhara; Hiroshi Ueki; Yuko Sakai-Tagawa; Amie J. Eisfeld; John J. Baczenas; David A. Baker; Shelby L. O’Connor; David H. O’Connor; Shuetsu Fukushi; Tsuguto Fujimoto; Yudai Kuroda; Aubree Gordon; Norio Ohmagari; Norio Sugaya; Hiroshi Yotsuyanagi; Hiroaki Mitsuya; Tadaki Suzuki; Yoshihiro Kawaoka. Characterization of a new SARS-CoV-2 variant that emerged in Brazil. Proceedings of the National Academy of Sciences 2021, 118, 1 .

AMA Style

Masaki Imai, Peter J. Halfmann, Seiya Yamayoshi, Kiyoko Iwatsuki-Horimoto, Shiho Chiba, Tokiko Watanabe, Noriko Nakajima, Mutsumi Ito, Makoto Kuroda, Maki Kiso, Tadashi Maemura, Kenta Takahashi, Samantha Loeber, Masato Hatta, Michiko Koga, Hiroyuki Nagai, Shinya Yamamoto, Makoto Saito, Eisuke Adachi, Osamu Akasaka, Morio Nakamura, Ichiro Nakachi, Takayuki Ogura, Rie Baba, Kensuke Fujita, Junichi Ochi, Keiko Mitamura, Hideaki Kato, Hideaki Nakajima, Kazuma Yagi, Shin-Ichiro Hattori, Kenji Maeda, Tetsuya Suzuki, Yusuke Miyazato, Riccardo Valdez, Carmen Gherasim, Yuri Furusawa, Moe Okuda, Michiko Ujie, Tiago J. S. Lopes, Atsuhiro Yasuhara, Hiroshi Ueki, Yuko Sakai-Tagawa, Amie J. Eisfeld, John J. Baczenas, David A. Baker, Shelby L. O’Connor, David H. O’Connor, Shuetsu Fukushi, Tsuguto Fujimoto, Yudai Kuroda, Aubree Gordon, Norio Ohmagari, Norio Sugaya, Hiroshi Yotsuyanagi, Hiroaki Mitsuya, Tadaki Suzuki, Yoshihiro Kawaoka. Characterization of a new SARS-CoV-2 variant that emerged in Brazil. Proceedings of the National Academy of Sciences. 2021; 118 (27):1.

Chicago/Turabian Style

Masaki Imai; Peter J. Halfmann; Seiya Yamayoshi; Kiyoko Iwatsuki-Horimoto; Shiho Chiba; Tokiko Watanabe; Noriko Nakajima; Mutsumi Ito; Makoto Kuroda; Maki Kiso; Tadashi Maemura; Kenta Takahashi; Samantha Loeber; Masato Hatta; Michiko Koga; Hiroyuki Nagai; Shinya Yamamoto; Makoto Saito; Eisuke Adachi; Osamu Akasaka; Morio Nakamura; Ichiro Nakachi; Takayuki Ogura; Rie Baba; Kensuke Fujita; Junichi Ochi; Keiko Mitamura; Hideaki Kato; Hideaki Nakajima; Kazuma Yagi; Shin-Ichiro Hattori; Kenji Maeda; Tetsuya Suzuki; Yusuke Miyazato; Riccardo Valdez; Carmen Gherasim; Yuri Furusawa; Moe Okuda; Michiko Ujie; Tiago J. S. Lopes; Atsuhiro Yasuhara; Hiroshi Ueki; Yuko Sakai-Tagawa; Amie J. Eisfeld; John J. Baczenas; David A. Baker; Shelby L. O’Connor; David H. O’Connor; Shuetsu Fukushi; Tsuguto Fujimoto; Yudai Kuroda; Aubree Gordon; Norio Ohmagari; Norio Sugaya; Hiroshi Yotsuyanagi; Hiroaki Mitsuya; Tadaki Suzuki; Yoshihiro Kawaoka. 2021. "Characterization of a new SARS-CoV-2 variant that emerged in Brazil." Proceedings of the National Academy of Sciences 118, no. 27: 1.

Immunology
Published: 17 May 2021 in Frontiers in Immunology
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Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) and is primarily transmitted by Aedes species mosquitoes; however, ZIKV can also be sexually transmitted. During the initial epidemic and in places where ZIKV is now considered endemic, it is difficult to disentangle the risks and contributions of sexual versus vector-borne transmission to adverse pregnancy outcomes. To examine the potential impact of sexual transmission of ZIKV on pregnancy outcome, we challenged three rhesus macaques (Macaca mulatta) three times intravaginally with 1 x 107 PFU of a low passage, African lineage ZIKV isolate (ZIKV-DAK) in the first trimester (~30 days gestational age). Samples were collected from all animals initially on days 3 through 10 post challenge, followed by twice, and then once weekly sample collection; ultrasound examinations were performed every 3-4 days then weekly as pregnancies progressed. All three dams had ZIKV RNA detectable in plasma on day 3 post-ZIKV challenge. At approximately 45 days gestation (17-18 days post-challenge), two of the three dams were found with nonviable embryos by ultrasound. Viral RNA was detected in recovered tissues and at the maternal-fetal interface (MFI) in both cases. The remaining viable pregnancy proceeded to near term (~155 days gestational age) and ZIKV RNA was detected at the MFI but not in fetal tissues. These results suggest that sexual transmission of ZIKV may represent an underappreciated risk of pregnancy loss during early gestation.

ACS Style

Christina M. Newman; Alice F. Tarantal; Michele L. Martinez; Heather A. Simmons; Terry K. Morgan; Xiankun Zeng; Jenna R. Rosinski; Mason I. Bliss; Ellie K. Bohm; Dawn M. Dudley; Matthew T. Aliota; Thomas C. Friedrich; Christopher J. Miller; David H. O’Connor. Early Embryonic Loss Following Intravaginal Zika Virus Challenge in Rhesus Macaques. Frontiers in Immunology 2021, 12, 1 .

AMA Style

Christina M. Newman, Alice F. Tarantal, Michele L. Martinez, Heather A. Simmons, Terry K. Morgan, Xiankun Zeng, Jenna R. Rosinski, Mason I. Bliss, Ellie K. Bohm, Dawn M. Dudley, Matthew T. Aliota, Thomas C. Friedrich, Christopher J. Miller, David H. O’Connor. Early Embryonic Loss Following Intravaginal Zika Virus Challenge in Rhesus Macaques. Frontiers in Immunology. 2021; 12 ():1.

Chicago/Turabian Style

Christina M. Newman; Alice F. Tarantal; Michele L. Martinez; Heather A. Simmons; Terry K. Morgan; Xiankun Zeng; Jenna R. Rosinski; Mason I. Bliss; Ellie K. Bohm; Dawn M. Dudley; Matthew T. Aliota; Thomas C. Friedrich; Christopher J. Miller; David H. O’Connor. 2021. "Early Embryonic Loss Following Intravaginal Zika Virus Challenge in Rhesus Macaques." Frontiers in Immunology 12, no. : 1.

Accepted manuscript
Published: 12 May 2021 in Clinical Infectious Diseases
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Background High-frequency, rapid-turnaround severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, 2 SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester, despite mandatory directly observed daily antigen testing. Methods During the fall 2020 semester, athletes and staff in both programs were tested daily using Quidel’s Sofia SARS Antigen Fluorescent Immunoassay, with positive antigen results requiring confirmatory testing with real-time reverse-transcription polymerase chain reaction. We used genomic sequencing to investigate transmission dynamics in these 2 outbreaks. Results In the first outbreak, 32 confirmed cases occurred within a university athletics program after the index patient attended a meeting while infectious, despite a negative antigen test on the day of the meeting. Among isolates sequenced from that outbreak, 24 (92%) of 26 were closely related, suggesting sustained transmission following an initial introduction event. In the second outbreak, 12 confirmed cases occurred among athletes from 2 university programs that faced each other in an athletic competition, despite receipt of negative antigen test results on the day of the competition. Sequences from both teams were closely related and distinct from viruses circulating in the community for team 1, suggesting transmission during intercollegiate competition in the community for team 2. Conclusions These findings suggest that antigen testing alone, even when mandated and directly observed, may not be sufficient as an intervention to prevent SARS-CoV-2 outbreaks in congregate settings, and they highlight the importance of vaccination to prevent SARS-CoV-2 outbreak in congregate settings.

ACS Style

Gage K Moreno; Katarina M Braun; Ian W Pray; Hannah E Segaloff; Ailam Lim; Keith Poulsen; Jonathan Meiman; James Borcher; Ryan P Westergaard; Michael K Moll; Thomas C Friedrich; David H O’Connor. Severe Acute Respiratory Syndrome Coronavirus 2 Transmission in Intercollegiate Athletics Not Fully Mitigated With Daily Antigen Testing. Clinical Infectious Diseases 2021, 73, S45 -S53.

AMA Style

Gage K Moreno, Katarina M Braun, Ian W Pray, Hannah E Segaloff, Ailam Lim, Keith Poulsen, Jonathan Meiman, James Borcher, Ryan P Westergaard, Michael K Moll, Thomas C Friedrich, David H O’Connor. Severe Acute Respiratory Syndrome Coronavirus 2 Transmission in Intercollegiate Athletics Not Fully Mitigated With Daily Antigen Testing. Clinical Infectious Diseases. 2021; 73 (Supplement):S45-S53.

Chicago/Turabian Style

Gage K Moreno; Katarina M Braun; Ian W Pray; Hannah E Segaloff; Ailam Lim; Keith Poulsen; Jonathan Meiman; James Borcher; Ryan P Westergaard; Michael K Moll; Thomas C Friedrich; David H O’Connor. 2021. "Severe Acute Respiratory Syndrome Coronavirus 2 Transmission in Intercollegiate Athletics Not Fully Mitigated With Daily Antigen Testing." Clinical Infectious Diseases 73, no. Supplement: S45-S53.

Preprint content
Published: 10 May 2021
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University settings have demonstrated potential for COVID-19 outbreaks, as they can combine congregate living, substantial social activity, and a young population predisposed to mild illness. Using genomic and epidemiologic data, we describe a COVID-19 outbreak at the University of Wisconsin (UW)–Madison. During August – October 2020, 3,485 students tested positive, including 856/6,162 students living in residence halls. Case counts began rising during move-in week for on-campus students (August 25-31, 2020), then rose rapidly during September 1-11, 2020. UW-Madison initiated multiple prevention efforts, including quarantining two residence halls; a subsequent decline in cases was observed. Genomic surveillance of cases from Dane County, where UW-Madison is located, did not find evidence of transmission from a large cluster of cases in the two residence halls quarantined during the outbreak. Coordinated implementation of prevention measures can effectively reduce SARS-CoV-2 spread in university settings and may limit spillover to the community surrounding the university.

ACS Style

Dustin W. Currie; Gage K. Moreno; Miranda J. Delahoy; Ian W. Pray; Amanda Jovaag; Katarina M. Braun; Devlin Cole; Todd Shechter; Geroncio C. Fajardo; Carol Griggs; Brian S. Yandell; Steve Goldstein; Dena Bushman; Hannah E. Segaloff; G. Patrick Kelly; Collin Pitts; Christine Lee; Katarina M. Grande; Amanda Kita-Yarbro; Brittany Grogan; Sara Mader; Jake Baggott; Allen C. Bateman; Ryan P. Westergaard; Jacqueline E. Tate; Thomas C. Friedrich; Hannah L. Kirking; David H. O’Connor; Marie E. Killerby. Description of a University COVID-19 Outbreak and Interventions to Disrupt Transmission, Wisconsin, August – October 2020. 2021, 1 .

AMA Style

Dustin W. Currie, Gage K. Moreno, Miranda J. Delahoy, Ian W. Pray, Amanda Jovaag, Katarina M. Braun, Devlin Cole, Todd Shechter, Geroncio C. Fajardo, Carol Griggs, Brian S. Yandell, Steve Goldstein, Dena Bushman, Hannah E. Segaloff, G. Patrick Kelly, Collin Pitts, Christine Lee, Katarina M. Grande, Amanda Kita-Yarbro, Brittany Grogan, Sara Mader, Jake Baggott, Allen C. Bateman, Ryan P. Westergaard, Jacqueline E. Tate, Thomas C. Friedrich, Hannah L. Kirking, David H. O’Connor, Marie E. Killerby. Description of a University COVID-19 Outbreak and Interventions to Disrupt Transmission, Wisconsin, August – October 2020. . 2021; ():1.

Chicago/Turabian Style

Dustin W. Currie; Gage K. Moreno; Miranda J. Delahoy; Ian W. Pray; Amanda Jovaag; Katarina M. Braun; Devlin Cole; Todd Shechter; Geroncio C. Fajardo; Carol Griggs; Brian S. Yandell; Steve Goldstein; Dena Bushman; Hannah E. Segaloff; G. Patrick Kelly; Collin Pitts; Christine Lee; Katarina M. Grande; Amanda Kita-Yarbro; Brittany Grogan; Sara Mader; Jake Baggott; Allen C. Bateman; Ryan P. Westergaard; Jacqueline E. Tate; Thomas C. Friedrich; Hannah L. Kirking; David H. O’Connor; Marie E. Killerby. 2021. "Description of a University COVID-19 Outbreak and Interventions to Disrupt Transmission, Wisconsin, August – October 2020." , no. : 1.

Journal article
Published: 07 April 2021 in Viruses
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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.

ACS Style

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 Style

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 (4):632.

Chicago/Turabian Style

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. 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.

Methodology article
Published: 12 March 2021 in BMC Genomics
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Background Oxford Nanopore Technologies’ instruments can sequence reads of great length. Long reads improve sequence assemblies by unambiguously spanning repetitive elements of the genome. Sequencing reads of significant length requires the preservation of long DNA template molecules through library preparation by pipetting reagents as slowly as possible to minimize shearing. This process is time-consuming and inconsistent at preserving read length as even small changes in volumetric flow rate can result in template shearing. Results We have designed SNAILS (Slow Nucleic Acid Instrument for Long Sequences), a 3D-printable instrument that automates slow pipetting of reagents used in long read library preparation for Oxford Nanopore sequencing. Across six sequencing libraries, SNAILS preserved more reads exceeding 100 kilobases in length and increased its libraries’ average read length over manual slow pipetting. Conclusions SNAILS is a low-cost, easily deployable solution for improving sequencing projects that require reads of significant length. By automating the slow pipetting of library preparation reagents, SNAILS increases the consistency and throughput of long read Nanopore sequencing.

ACS Style

Trent M. Prall; Emma K. Neumann; Julie A. Karl; Cecilia G. Shortreed; David A. Baker; Hailey E. Bussan; Roger W. Wiseman; David Oconnor. Consistent ultra-long DNA sequencing with automated slow pipetting. BMC Genomics 2021, 22, 1 -12.

AMA Style

Trent M. Prall, Emma K. Neumann, Julie A. Karl, Cecilia G. Shortreed, David A. Baker, Hailey E. Bussan, Roger W. Wiseman, David Oconnor. Consistent ultra-long DNA sequencing with automated slow pipetting. BMC Genomics. 2021; 22 (1):1-12.

Chicago/Turabian Style

Trent M. Prall; Emma K. Neumann; Julie A. Karl; Cecilia G. Shortreed; David A. Baker; Hailey E. Bussan; Roger W. Wiseman; David Oconnor. 2021. "Consistent ultra-long DNA sequencing with automated slow pipetting." BMC Genomics 22, no. 1: 1-12.

Preprint content
Published: 06 March 2021
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Background High frequency, rapid turnaround SARS-CoV-2 testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, two SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester despite mandatory directly observed daily antigen testing. Methods During the fall 2020 semester, athletes and staff in both programs were tested daily using Quidel’s Sofia SARS Antigen Fluorescent Immunoassay (FIA), with positive antigen results requiring confirmatory testing with real-time reverse transcription polymerase chain reaction (RT-PCR). We used genomic sequencing to investigate transmission dynamics in these two outbreaks. Results In Outbreak 1, 32 confirmed cases occurred within a university athletics program after the index patient attended a meeting while infectious despite a negative antigen test on the day of the meeting. Among isolates sequenced from Outbreak 1, 24 (92%) of 26 were closely related, suggesting sustained transmission following an initial introduction event. In Outbreak 2, 12 confirmed cases occurred among athletes from two university programs that faced each other in an athletic competition despite receiving negative antigen test results on the day of the competition. Sequences from both teams were closely related and unique from strains circulating in the community, suggesting transmission during intercollegiate competition. Conclusions These findings suggest that antigen testing alone, even when mandated and directly observed, may not be sufficient as an intervention to prevent SARS-CoV-2 outbreaks in congregate settings, and highlights the importance of supplementing serial antigen testing with appropriate mitigation strategies to prevent SARS-CoV-2 outbreak in congregate settings. Summary High frequency, rapid turnaround SARS-CoV-2 testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, here we describe two SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester.

ACS Style

Gage K. Moreno; Katarina M. Braun; Ian W. Pray; Hannah E. Segaloff; Ailam Lim; Keith Poulson; Jonathan Meiman; James Borcher; Ryan P. Westergaard; Michael K. Moll; Thomas C. Friedrich; David H. O’Connor. SARS-CoV-2 transmission in intercollegiate athletics not fully mitigated with daily antigen testing. 2021, 1 .

AMA Style

Gage K. Moreno, Katarina M. Braun, Ian W. Pray, Hannah E. Segaloff, Ailam Lim, Keith Poulson, Jonathan Meiman, James Borcher, Ryan P. Westergaard, Michael K. Moll, Thomas C. Friedrich, David H. O’Connor. SARS-CoV-2 transmission in intercollegiate athletics not fully mitigated with daily antigen testing. . 2021; ():1.

Chicago/Turabian Style

Gage K. Moreno; Katarina M. Braun; Ian W. Pray; Hannah E. Segaloff; Ailam Lim; Keith Poulson; Jonathan Meiman; James Borcher; Ryan P. Westergaard; Michael K. Moll; Thomas C. Friedrich; David H. O’Connor. 2021. "SARS-CoV-2 transmission in intercollegiate athletics not fully mitigated with daily antigen testing." , no. : 1.

Research article
Published: 26 February 2021 in PLOS Pathogens
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The evolutionary mechanisms by which SARS-CoV-2 viruses adapt to mammalian hosts and, potentially, undergo antigenic evolution depend on the ways genetic variation is generated and selected within and between individual hosts. Using domestic cats as a model, we show that SARS-CoV-2 consensus sequences remain largely unchanged over time within hosts, while dynamic sub-consensus diversity reveals processes of genetic drift and weak purifying selection. We further identify a notable variant at amino acid position 655 in Spike (H655Y), which was previously shown to confer escape from human monoclonal antibodies. This variant arises rapidly and persists at intermediate frequencies in index cats. It also becomes fixed following transmission in two of three pairs. These dynamics suggest this site may be under positive selection in this system and illustrate how a variant can quickly arise and become fixed in parallel across multiple transmission pairs. Transmission of SARS-CoV-2 in cats involved a narrow bottleneck, with new infections founded by fewer than ten viruses. In RNA virus evolution, stochastic processes like narrow transmission bottlenecks and genetic drift typically act to constrain the overall pace of adaptive evolution. Our data suggest that here, positive selection in index cats followed by a narrow transmission bottleneck may have instead accelerated the fixation of S H655Y, a potentially beneficial SARS-CoV-2 variant. Overall, our study suggests species- and context-specific adaptations are likely to continue to emerge. This underscores the importance of continued genomic surveillance for new SARS-CoV-2 variants as well as heightened scrutiny for signatures of SARS-CoV-2 positive selection in humans and mammalian model systems.

ACS Style

Katarina M. Braun; Gage K. Moreno; Peter J. Halfmann; Emma B. Hodcroft; David A. Baker; Emma C. Boehm; Andrea M. Weiler; Amelia K. Haj; Masato Hatta; Shiho Chiba; Tadashi Maemura; Yoshihiro Kawaoka; Katia Koelle; David H. O’Connor; Thomas C. Friedrich. Transmission of SARS-CoV-2 in domestic cats imposes a narrow bottleneck. PLOS Pathogens 2021, 17, e1009373 .

AMA Style

Katarina M. Braun, Gage K. Moreno, Peter J. Halfmann, Emma B. Hodcroft, David A. Baker, Emma C. Boehm, Andrea M. Weiler, Amelia K. Haj, Masato Hatta, Shiho Chiba, Tadashi Maemura, Yoshihiro Kawaoka, Katia Koelle, David H. O’Connor, Thomas C. Friedrich. Transmission of SARS-CoV-2 in domestic cats imposes a narrow bottleneck. PLOS Pathogens. 2021; 17 (2):e1009373.

Chicago/Turabian Style

Katarina M. Braun; Gage K. Moreno; Peter J. Halfmann; Emma B. Hodcroft; David A. Baker; Emma C. Boehm; Andrea M. Weiler; Amelia K. Haj; Masato Hatta; Shiho Chiba; Tadashi Maemura; Yoshihiro Kawaoka; Katia Koelle; David H. O’Connor; Thomas C. Friedrich. 2021. "Transmission of SARS-CoV-2 in domestic cats imposes a narrow bottleneck." PLOS Pathogens 17, no. 2: e1009373.

Preprint content
Published: 01 February 2021
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Summary Background Healthcare personnel (HCP) are at increased risk of infection with the severe acute respiratory coronavirus 2019 virus (SARS-CoV-2). Between 12 March 2020 and 10 January 2021, >1,170 HCP tested positive for SARS-CoV-2 at a major academic medical institution in the Upper Midwest of the United States. We aimed to understand the sources of infections in HCP and to evaluate the efficacy of infection control procedures used at this institution to protect HCP from healthcare-associated transmission. Methods In this retrospective case series, we used viral genomics to investigate the likely source of SARS-CoV-2 infection in 96 HCP where epidemiological data alone could not be used to rule out healthcare-associated transmission. We obtained limited epidemiological data through informal interviews and review of the electronic health record. We combined viral sequence data and available epidemiological information to infer the most likely source of HCP infection. Findings We investigated 32 SARS-CoV-2 infection clusters involving 96 HCP, 140 possible patient contacts, and 1 household contact (total n = 237). Of these, 182 sequences met quality standards and were used for downstream analysis. We found the majority of HCP infections could not be linked to a patient or co-worker and therefore likely occurred in the outside community (58/96; 60.4%). We found a smaller percentage could be traced to a coworker (10/96; 10.4%) or were part of a patient-employee cluster (12/96; 12.5%). Strikingly, the smallest proportion of HCP infections could be clearly traced to a patient source (4/96; 4.2%). Interpretation Infection control procedures, consistently followed, offer significant protection to HCP caring for COVID-19 patients in a representative American academic medical institution. Rapid SARS-CoV-2 genome sequencing in healthcare settings can be used retrospectively to reconstruct the likely source of HCP infection when epidemiological data are not available or are inconclusive. Understanding the source of SARS-CoV-2 infection can then be used prospectively to adjust and improve infection control practices and guidelines. Funding This project was funded in part through a COVID-19 Response grant from the Wisconsin Partnership Program at the University of Wisconsin School of Medicine and Public Health to T.C.F. and D.H.O. Author N.S. is supported by the National Institute of Allergy and Infectious Diseases Institute (NIAID) Grant 1DP2AI144244-01. Research in context Evidence before this study On 16 January 2021 we searched for “SARS-CoV-2” AND “healthcare workers” AND “viral sequencing” in Google Scholar. This search returned 57 results, and included a number of preprint articles. We found two studies that used viral sequencing to investigate healthcare-associated outbreaks in the Netherlands 1 and the United Kingdom 2. To our knowledge, no study has used viral sequencing to specifically investigate the source of SARS-CoV-2 infections in healthcare workers in the United States. Although we and others have written about the potential utility of sequencing as an infection control asset 3–6, few have demonstrated the practical application of such efforts. Added value of this study Our study suggests infection control measures in place at the institution evaluated in this case series are largely protecting healthcare personnel (HCP) from healthcare-associated SARS-CoV-2 infections. Even so, the majority of healthcare-associated infections we did identify appeared to be linked to HCP-to-HCP spread so additional messaging and guidelines to reduce HCP-to-HCP spread in and out of the workplace may be warranted. In addition, we demonstrated how rapid viral sequencing can be combined with, even limited, epidemiological information to reconstruct healthcare-associated SARS-CoV-2 outbreaks. Implications of all the available evidence Healthcare-associated SARS-CoV-2 infections negatively affect HCP, patients, and communities. Infections among HCP add further strain to the healthcare system and put patients and other HCP at risk. We found the majority of HCP infections appeared to be acquired through community exposure so measures to reduce community spread are critical. This further emphasizes the importance of mask-wearing, physical distancing, robust testing programs, and the rapid distribution of vaccines.

ACS Style

Katarina M. Braun; Gage K. Moreno; Ashley Buys; Max Bobholz; Molly A. Accola; Laura Anderson; William M. Rehrauer; David A. Baker; Nasia Safdar; Alexander J. Lepak; David H. O’Connor; Thomas C. Friedrich. Viral sequencing reveals US healthcare personnel rarely become infected with SARS-CoV-2 through patient contact. 2021, 1 .

AMA Style

Katarina M. Braun, Gage K. Moreno, Ashley Buys, Max Bobholz, Molly A. Accola, Laura Anderson, William M. Rehrauer, David A. Baker, Nasia Safdar, Alexander J. Lepak, David H. O’Connor, Thomas C. Friedrich. Viral sequencing reveals US healthcare personnel rarely become infected with SARS-CoV-2 through patient contact. . 2021; ():1.

Chicago/Turabian Style

Katarina M. Braun; Gage K. Moreno; Ashley Buys; Max Bobholz; Molly A. Accola; Laura Anderson; William M. Rehrauer; David A. Baker; Nasia Safdar; Alexander J. Lepak; David H. O’Connor; Thomas C. Friedrich. 2021. "Viral sequencing reveals US healthcare personnel rarely become infected with SARS-CoV-2 through patient contact." , no. : 1.

Research article
Published: 17 December 2020 in Science
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The rhesus macaque (Macaca mulatta) is the most widely studied nonhuman primate (NHP) in biomedical research. We present an updated reference genome assembly (Mmul_10, contig N50 = 46 Mbp) that increases the sequence contiguity 120-fold and annotate it using 6.5 million full-length transcripts, thus improving our understanding of gene content, isoform diversity, and repeat organization. With the improved assembly of segmental duplications, we discovered new lineage-specific genes and expanded gene families that are potentially informative in studies of evolution and disease susceptibility. Whole-genome sequencing (WGS) data from 853 rhesus macaques identified 85.7 million single-nucleotide variants (SNVs) and 10.5 million indel variants, including potentially damaging variants in genes associated with human autism and developmental delay, providing a framework for developing noninvasive NHP models of human disease.

ACS Style

Wesley C. Warren; R. Alan Harris; Marina Haukness; Ian T. Fiddes; Shwetha C. Murali; Jason Fernandes; Philip C. Dishuck; Jessica M. Storer; Muthuswamy Raveendran; LaDeana W. Hillier; David Porubsky; Yafei Mao; David Gordon; Mitchell R. Vollger; Alexandra P. Lewis; Katherine M. Munson; Elizabeth DeVogelaere; Joel Armstrong; Mark Diekhans; Jerilyn A. Walker; Chad Tomlinson; Tina A. Graves-Lindsay; Milinn Kremitzki; Sofie R. Salama; Peter A. Audano; Merly Escalona; Nicholas W. Maurer; Francesca Antonacci; Ludovica Mercuri; Flavia A. M. Maggiolini; Claudia Rita Catacchio; Jason G. Underwood; David H. O’Connor; Ashley D. Sanders; Jan O. Korbel; Betsy Ferguson; H. Michael Kubisch; Louis Picker; Ned H. Kalin; Douglas Rosene; Jon Levine; David H. Abbott; Stanton B. Gray; Mar M. Sanchez; Zsofia A. Kovacs-Balint; Joseph W. Kemnitz; Sara M. Thomasy; Jeffrey A. Roberts; Erin L. Kinnally; John P. Capitanio; J. H. Pate Skene; Michael Platt; Shelley A. Cole; Richard E. Green; Mario Ventura; Roger W. Wiseman; Benedict Paten; Mark A. Batzer; Jeffrey Rogers; Evan E. Eichler. Sequence diversity analyses of an improved rhesus macaque genome enhance its biomedical utility. Science 2020, 370, eabc6617 .

AMA Style

Wesley C. Warren, R. Alan Harris, Marina Haukness, Ian T. Fiddes, Shwetha C. Murali, Jason Fernandes, Philip C. Dishuck, Jessica M. Storer, Muthuswamy Raveendran, LaDeana W. Hillier, David Porubsky, Yafei Mao, David Gordon, Mitchell R. Vollger, Alexandra P. Lewis, Katherine M. Munson, Elizabeth DeVogelaere, Joel Armstrong, Mark Diekhans, Jerilyn A. Walker, Chad Tomlinson, Tina A. Graves-Lindsay, Milinn Kremitzki, Sofie R. Salama, Peter A. Audano, Merly Escalona, Nicholas W. Maurer, Francesca Antonacci, Ludovica Mercuri, Flavia A. M. Maggiolini, Claudia Rita Catacchio, Jason G. Underwood, David H. O’Connor, Ashley D. Sanders, Jan O. Korbel, Betsy Ferguson, H. Michael Kubisch, Louis Picker, Ned H. Kalin, Douglas Rosene, Jon Levine, David H. Abbott, Stanton B. Gray, Mar M. Sanchez, Zsofia A. Kovacs-Balint, Joseph W. Kemnitz, Sara M. Thomasy, Jeffrey A. Roberts, Erin L. Kinnally, John P. Capitanio, J. H. Pate Skene, Michael Platt, Shelley A. Cole, Richard E. Green, Mario Ventura, Roger W. Wiseman, Benedict Paten, Mark A. Batzer, Jeffrey Rogers, Evan E. Eichler. Sequence diversity analyses of an improved rhesus macaque genome enhance its biomedical utility. Science. 2020; 370 (6523):eabc6617.

Chicago/Turabian Style

Wesley C. Warren; R. Alan Harris; Marina Haukness; Ian T. Fiddes; Shwetha C. Murali; Jason Fernandes; Philip C. Dishuck; Jessica M. Storer; Muthuswamy Raveendran; LaDeana W. Hillier; David Porubsky; Yafei Mao; David Gordon; Mitchell R. Vollger; Alexandra P. Lewis; Katherine M. Munson; Elizabeth DeVogelaere; Joel Armstrong; Mark Diekhans; Jerilyn A. Walker; Chad Tomlinson; Tina A. Graves-Lindsay; Milinn Kremitzki; Sofie R. Salama; Peter A. Audano; Merly Escalona; Nicholas W. Maurer; Francesca Antonacci; Ludovica Mercuri; Flavia A. M. Maggiolini; Claudia Rita Catacchio; Jason G. Underwood; David H. O’Connor; Ashley D. Sanders; Jan O. Korbel; Betsy Ferguson; H. Michael Kubisch; Louis Picker; Ned H. Kalin; Douglas Rosene; Jon Levine; David H. Abbott; Stanton B. Gray; Mar M. Sanchez; Zsofia A. Kovacs-Balint; Joseph W. Kemnitz; Sara M. Thomasy; Jeffrey A. Roberts; Erin L. Kinnally; John P. Capitanio; J. H. Pate Skene; Michael Platt; Shelley A. Cole; Richard E. Green; Mario Ventura; Roger W. Wiseman; Benedict Paten; Mark A. Batzer; Jeffrey Rogers; Evan E. Eichler. 2020. "Sequence diversity analyses of an improved rhesus macaque genome enhance its biomedical utility." Science 370, no. 6523: eabc6617.

Communication
Published: 14 December 2020 in Viruses
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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.

ACS Style

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 Style

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 (12):1436.

Chicago/Turabian Style

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. 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.

Journal article
Published: 18 November 2020 in The Journal of Immunology
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The rhesus macaque is an important animal model for AIDS and other infectious diseases. However, the investigation of Fc-mediated Ab responses in macaques is complicated by species-specific differences in FcγRs and IgG subclasses relative to humans. To assess the effects of these differences on FcγR–IgG interactions, reporter cell lines expressing common allotypes of human and rhesus macaque FcγR2A and FcγR3A were established. FcγR-mediated responses to B cells were measured in the presence of serial dilutions of anti-CD20 Abs with Fc domains corresponding to each of the four subclasses of human and rhesus IgG and with Fc variants of IgG1 that enhance binding to FcγR2A or FcγR3A. All of the FcγRs were functional and preferentially recognized either IgG1 or IgG2. Whereas allotypes of rhesus FcγR2A were identified with responses similar to variants of human FcγR2A with higher (H131) and lower (R131) affinity for IgG, all of the rhesus FcγR3A allotypes exhibited responses most similar to the higher affinity V158 variant of human FcγR3A. Unlike responses to human IgGs, there was little variation in FcγR-mediated responses to different subclasses of rhesus IgG. Phylogenetic comparisons suggest that this reflects limited sequence variation of macaque IgGs as a result of their relatively recent diversification from a common IGHG gene since humans and macaques last shared a common ancestor. These findings reveal species-specific differences in FcγR–IgG interactions with important implications for investigating Ab effector functions in macaques.

ACS Style

Michael W. Grunst; Andres G. Grandea; Sanath Kumar Janaka; Iman Hammad; Parker Grimes; Julie A. Karl; Roger Wiseman; David H. O’Connor; David T. Evans. Functional Interactions of Common Allotypes of Rhesus Macaque FcγR2A and FcγR3A with Human and Macaque IgG Subclasses. The Journal of Immunology 2020, 205, 3319 -3332.

AMA Style

Michael W. Grunst, Andres G. Grandea, Sanath Kumar Janaka, Iman Hammad, Parker Grimes, Julie A. Karl, Roger Wiseman, David H. O’Connor, David T. Evans. Functional Interactions of Common Allotypes of Rhesus Macaque FcγR2A and FcγR3A with Human and Macaque IgG Subclasses. The Journal of Immunology. 2020; 205 (12):3319-3332.

Chicago/Turabian Style

Michael W. Grunst; Andres G. Grandea; Sanath Kumar Janaka; Iman Hammad; Parker Grimes; Julie A. Karl; Roger Wiseman; David H. O’Connor; David T. Evans. 2020. "Functional Interactions of Common Allotypes of Rhesus Macaque FcγR2A and FcγR3A with Human and Macaque IgG Subclasses." The Journal of Immunology 205, no. 12: 3319-3332.

Preprint content
Published: 17 November 2020
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The evolutionary mechanisms by which SARS-CoV-2 viruses adapt to mammalian hosts and, potentially, undergo antigenic evolution depend on the ways genetic variation is generated and selected within and between individual hosts. Using domestic cats as a model, we show that SARS-CoV-2 consensus sequences remain largely unchanged over time within hosts, while dynamic sub-consensus diversity reveals processes of genetic drift and weak purifying selection. We further identify a notable variant at amino acid position 655 in Spike (H655Y), which was previously shown to confer escape from human monoclonal antibodies. This variant arises rapidly and persists at intermediate frequencies in index cats. It also becomes fixed following transmission in two of three pairs. These dynamics suggest this site may be under positive selection in this system and illustrate how a variant can quickly arise and become fixed in parallel across multiple transmission pairs. Transmission of SARS-CoV-2 in cats involved a narrow bottleneck, with new infections founded by fewer than ten viruses. In RNA virus evolution, stochastic processes like narrow transmission bottlenecks and genetic drift typically act to constrain the overall pace of adaptive evolution. Our data suggest that here, positive selection in index cats followed by a narrow transmission bottleneck may have instead accelerated the fixation of S H655Y, a potentially beneficial SARS-CoV-2 variant. Overall, our study suggests species- and context-specific adaptations are likely to continue to emerge. This underscores the importance of continued genomic surveillance for new SARS-CoV-2 variants as well as heightened scrutiny for signatures of SARS-CoV-2 positive selection in humans and mammalian model systems. Author summary Through ongoing human adaptation, spill-back events from other animal intermediates, or with the distribution of vaccines and therapeutics, the landscape of SARS-CoV-2 genetic variation is certain to change. The evolutionary mechanisms by which SARS-CoV-2 will continue to adapt to mammalian hosts depend on genetic variation generated within and between hosts. Here, using domestic cats as a model, we show that within-host SARS-CoV-2 genetic variation is predominantly influenced by genetic drift and purifying selection. Transmission of SARS-CoV-2 between hosts is defined by a narrow transmission bottleneck, involving 2-5 viruses. We further identify a notable variant at amino acid position 655 in Spike (H655Y), which arises rapidly and is transmitted in cats. Spike H655Y has been previously shown to confer escape from human monoclonal antibodies and is currently found in over 1000 human sequences. Overall, our study suggests species- and context-specific adaptations are likely to continue to emerge, underscoring the importance of continued genomic surveillance in humans and non-human mammalian hosts.

ACS Style

Katarina M. Braun; Gage K. Moreno; Peter J. Halfmann; Emma B. Hodcroft; David A. Baker; Emma C. Boehm; Andrea M. Weiler; Amelia K. Haj; Masato Hatta; Shiho Chiba; Tadashi Maemura; Yoshihiro Kawaoka; Katia Koelle; David H. O’Connor; Thomas C. Friedrich. Transmission of SARS-CoV-2 in domestic cats imposes a narrow bottleneck. 2020, 1 .

AMA Style

Katarina M. Braun, Gage K. Moreno, Peter J. Halfmann, Emma B. Hodcroft, David A. Baker, Emma C. Boehm, Andrea M. Weiler, Amelia K. Haj, Masato Hatta, Shiho Chiba, Tadashi Maemura, Yoshihiro Kawaoka, Katia Koelle, David H. O’Connor, Thomas C. Friedrich. Transmission of SARS-CoV-2 in domestic cats imposes a narrow bottleneck. . 2020; ():1.

Chicago/Turabian Style

Katarina M. Braun; Gage K. Moreno; Peter J. Halfmann; Emma B. Hodcroft; David A. Baker; Emma C. Boehm; Andrea M. Weiler; Amelia K. Haj; Masato Hatta; Shiho Chiba; Tadashi Maemura; Yoshihiro Kawaoka; Katia Koelle; David H. O’Connor; Thomas C. Friedrich. 2020. "Transmission of SARS-CoV-2 in domestic cats imposes a narrow bottleneck." , no. : 1.

Journal article
Published: 03 November 2020 in Nature Communications
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Evidence-based public health approaches that minimize the introduction and spread of new SARS-CoV-2 transmission clusters are urgently needed in the United States and other countries struggling with expanding epidemics. Here we analyze 247 full-genome SARS-CoV-2 sequences from two nearby communities in Wisconsin, USA, and find surprisingly distinct patterns of viral spread. Dane County had the 12th known introduction of SARS-CoV-2 in the United States, but this did not lead to descendant community spread. Instead, the Dane County outbreak was seeded by multiple later introductions, followed by limited community spread. In contrast, relatively few introductions in Milwaukee County led to extensive community spread. We present evidence for reduced viral spread in both counties following the statewide “Safer at Home” order, which went into effect 25 March 2020. Our results suggest patterns of SARS-CoV-2 transmission may vary substantially even in nearby communities. Understanding these local patterns will enable better targeting of public health interventions.

ACS Style

Gage K. Moreno; Katarina M. Braun; Kasen K. Riemersma; Michael A. Martin; Peter J. Halfmann; Chelsea M. Crooks; Trent Prall; David Baker; John J. Baczenas; Anna S. Heffron; Mitchell Ramuta; Manjeet Khubbar; Andrea M. Weiler; Molly A. Accola; William M. Rehrauer; Shelby L. O’Connor; Nasia Safdar; Caitlin S. Pepperell; Trivikram Dasu; Sanjib Bhattacharyya; Yoshihiro Kawaoka; Katia Koelle; David H. O’Connor; Thomas C. Friedrich. Revealing fine-scale spatiotemporal differences in SARS-CoV-2 introduction and spread. Nature Communications 2020, 11, 1 -13.

AMA Style

Gage K. Moreno, Katarina M. Braun, Kasen K. Riemersma, Michael A. Martin, Peter J. Halfmann, Chelsea M. Crooks, Trent Prall, David Baker, John J. Baczenas, Anna S. Heffron, Mitchell Ramuta, Manjeet Khubbar, Andrea M. Weiler, Molly A. Accola, William M. Rehrauer, Shelby L. O’Connor, Nasia Safdar, Caitlin S. Pepperell, Trivikram Dasu, Sanjib Bhattacharyya, Yoshihiro Kawaoka, Katia Koelle, David H. O’Connor, Thomas C. Friedrich. Revealing fine-scale spatiotemporal differences in SARS-CoV-2 introduction and spread. Nature Communications. 2020; 11 (1):1-13.

Chicago/Turabian Style

Gage K. Moreno; Katarina M. Braun; Kasen K. Riemersma; Michael A. Martin; Peter J. Halfmann; Chelsea M. Crooks; Trent Prall; David Baker; John J. Baczenas; Anna S. Heffron; Mitchell Ramuta; Manjeet Khubbar; Andrea M. Weiler; Molly A. Accola; William M. Rehrauer; Shelby L. O’Connor; Nasia Safdar; Caitlin S. Pepperell; Trivikram Dasu; Sanjib Bhattacharyya; Yoshihiro Kawaoka; Katia Koelle; David H. O’Connor; Thomas C. Friedrich. 2020. "Revealing fine-scale spatiotemporal differences in SARS-CoV-2 introduction and spread." Nature Communications 11, no. 1: 1-13.

Preprint content
Published: 11 October 2020
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The search for potential antibody-based diagnostics, vaccines, and therapeutics for pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused almost exclusively on the spike (S) and nucleocapsid (N) proteins. Coronavirus membrane (M), ORF3a, and ORF8 proteins are humoral immunogens in other coronaviruses (CoVs) but remain largely uninvestigated for SARS-CoV-2. Here we use ultradense peptide microarray mapping to show that SARS-CoV-2 infection induces robust antibody responses to epitopes throughout the SARS-CoV-2 proteome, particularly in M, in which one epitope achieved excellent diagnostic accuracy. We map 79 B cell epitopes throughout the SARS-CoV-2 proteome and demonstrate that antibodies that develop in response to SARS-CoV-2 infection bind homologous peptide sequences in the six other known human CoVs. We also confirm reactivity against four of our top-ranking epitopes by enzyme-linked immunosorbent assay (ELISA). Illness severity correlated with increased reactivity to nine SARS-CoV-2 epitopes in S, M, N, and ORF3a in our population. Our results demonstrate previously unknown, highly reactive B cell epitopes throughout the full proteome of SARS-CoV-2 and other CoV proteins.

ACS Style

Anna S. Heffron; Sean J. McIlwain; Maya F. Amjadi; David A. Baker; Saniya Khullar; Ajay K. Sethi; Ann C. Palmenberg; Miriam A. Shelef; David H. O’Connor; Irene M. Ong. The landscape of antibody binding in SARS-CoV-2 infection. 2020, 1 .

AMA Style

Anna S. Heffron, Sean J. McIlwain, Maya F. Amjadi, David A. Baker, Saniya Khullar, Ajay K. Sethi, Ann C. Palmenberg, Miriam A. Shelef, David H. O’Connor, Irene M. Ong. The landscape of antibody binding in SARS-CoV-2 infection. . 2020; ():1.

Chicago/Turabian Style

Anna S. Heffron; Sean J. McIlwain; Maya F. Amjadi; David A. Baker; Saniya Khullar; Ajay K. Sethi; Ann C. Palmenberg; Miriam A. Shelef; David H. O’Connor; Irene M. Ong. 2020. "The landscape of antibody binding in SARS-CoV-2 infection." , no. : 1.

Journal article
Published: 30 September 2020 in Microorganisms
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From 2010 to 2015, 73 common marmosets (Callithrix jacchus) housed at the Wisconsin National Primate Research Center (WNPRC) were diagnosed postmortem with lymphocytic enterocolitis. We used unbiased deep-sequencing to screen the blood of deceased enterocolitis-positive marmosets for viruses. In five out of eight common marmosets with lymphocytic enterocolitis, we discovered a novel pegivirus not present in ten matched, clinically normal controls. The novel virus, which we named Southwest bike trail virus (SOBV), is most closely related (68% nucleotide identity) to a strain of simian pegivirus A isolated from a three-striped night monkey (Aotus trivirgatus). We screened 146 living WNPRC common marmosets for SOBV, finding an overall prevalence of 34% (50/146). Over four years, 85 of these 146 animals died or were euthanized. Histological examination revealed 27 SOBV-positive marmosets from this cohort had lymphocytic enterocolitis, compared to 42 SOBV-negative marmosets, indicating no association between SOBV and disease in this cohort (p = 0.0798). We also detected SOBV in two of 33 (6%) clinically normal marmosets screened during transfer from the New England Primate Research Center, suggesting SOBV could be exerting confounding influences on comparisons of common marmoset studies from multiple colonies.

ACS Style

Anna S. Heffron; Michael Lauck; Elizabeth D. Somsen; Elizabeth C. Townsend; Adam L. Bailey; Megan Sosa; Jens Eickhoff; Saverio Capuano Iii; Christina M. Newman; Jens H. Kuhn; Andres Mejia; Heather A. Simmons; David H. O’Connor. Discovery of a Novel Simian Pegivirus in Common Marmosets (Callithrix jacchus) with Lymphocytic Enterocolitis. Microorganisms 2020, 8, 1509 .

AMA Style

Anna S. Heffron, Michael Lauck, Elizabeth D. Somsen, Elizabeth C. Townsend, Adam L. Bailey, Megan Sosa, Jens Eickhoff, Saverio Capuano Iii, Christina M. Newman, Jens H. Kuhn, Andres Mejia, Heather A. Simmons, David H. O’Connor. Discovery of a Novel Simian Pegivirus in Common Marmosets (Callithrix jacchus) with Lymphocytic Enterocolitis. Microorganisms. 2020; 8 (10):1509.

Chicago/Turabian Style

Anna S. Heffron; Michael Lauck; Elizabeth D. Somsen; Elizabeth C. Townsend; Adam L. Bailey; Megan Sosa; Jens Eickhoff; Saverio Capuano Iii; Christina M. Newman; Jens H. Kuhn; Andres Mejia; Heather A. Simmons; David H. O’Connor. 2020. "Discovery of a Novel Simian Pegivirus in Common Marmosets (Callithrix jacchus) with Lymphocytic Enterocolitis." Microorganisms 8, no. 10: 1509.