Journal article
Determinants of pegivirus persistence, cross-species infection, and adaptation in the laboratory mouse
PLoS pathogens, Vol.20(8), e1012436
08/28/2024
DOI: 10.1371/journal.ppat.1012436
PMCID: PMC11355568
PMID: 39196893
Abstract
Viruses capable of causing persistent infection have developed sophisticated mechanisms for evading host immunity, and understanding these processes can reveal novel features of the host immune system. One such virus, human pegivirus (HPgV), infects ~15% of the global human population, but little is known about its biology beyond the fact that it does not cause overt disease. We passaged a pegivirus isolate of feral brown rats (RPgV) in immunodeficient laboratory mice to develop a mouse-adapted virus (maPgV) that established persistent high-titer infection in a majority of wild-type laboratory mice. maRPgV viremia was detected in the blood of mice for >300 days without apparent disease, closely recapitulating the hallmarks of HPgV infection in humans. We found a pro-viral role for type-I interferon in chronic infection; a lack of PD-1-mediated tolerance to PgV infection; and multiple mechanisms by which PgV immunity can be achieved by an immunocompetent host. These data indicate that the PgV immune evasion strategy has aspects that are both common and unique among persistent viral infections. The creation of maPgV represents the first PgV infection model in wild-type mice, thus opening the entire toolkit of the mouse host to enable further investigation of this persistent RNA virus infections.Viruses capable of causing persistent infection have developed sophisticated mechanisms for evading host immunity, and understanding these processes can reveal novel features of the host immune system. One such virus, human pegivirus (HPgV), infects ~15% of the global human population, but little is known about its biology beyond the fact that it does not cause overt disease. We passaged a pegivirus isolate of feral brown rats (RPgV) in immunodeficient laboratory mice to develop a mouse-adapted virus (maPgV) that established persistent high-titer infection in a majority of wild-type laboratory mice. maRPgV viremia was detected in the blood of mice for >300 days without apparent disease, closely recapitulating the hallmarks of HPgV infection in humans. We found a pro-viral role for type-I interferon in chronic infection; a lack of PD-1-mediated tolerance to PgV infection; and multiple mechanisms by which PgV immunity can be achieved by an immunocompetent host. These data indicate that the PgV immune evasion strategy has aspects that are both common and unique among persistent viral infections. The creation of maPgV represents the first PgV infection model in wild-type mice, thus opening the entire toolkit of the mouse host to enable further investigation of this persistent RNA virus infections.
Details
- Title: Subtitle
- Determinants of pegivirus persistence, cross-species infection, and adaptation in the laboratory mouse
- Creators
- Kylie Nennig - University of Wisconsin–MadisonSatyapramod Murthy - Nationwide Children's HospitalSara Maloney - University of Wisconsin–MadisonTeressa M Shaw - University of Wisconsin–MadisonMark Sharobim - University of Wisconsin–MadisonEduard Matkovic - University of Wisconsin–MadisonSimi Fadiran - University of Wisconsin–MadisonMalorie Larsen - University of Wisconsin–MadisonMitchell D Ramuta - University of Wisconsin–MadisonArthur S Kim - Scripps Research InstituteJohn R Teijaro - Scripps Research InstituteJoe Grove - MRC University of Glasgow Centre for Virus ResearchMatthew Stremlau - Johns Hopkins UniversityHimanshu Sharma - Nationwide Children's HospitalSheetal Trivedi - Nationwide Children's HospitalMichael J Blum - University of Tennessee at KnoxvilleDavid H O'ConnorJennifer L Hyde - University of WashingtonJack T Stapleton - Iowa City VA Health Care SystemAmit Kapoor - The Ohio State UniversityAdam L Bailey - University of Wisconsin–Madison
- Resource Type
- Journal article
- Publication Details
- PLoS pathogens, Vol.20(8), e1012436
- Publisher
- PUBLIC LIBRARY SCIENCE
- DOI
- 10.1371/journal.ppat.1012436
- PMID
- 39196893
- PMCID
- PMC11355568
- ISSN
- 1553-7374
- eISSN
- 1553-7374
- Grant note
- Royal Society: 107653/Z/15/Z MRC-University of Glasgow Centre for Virus Research from the Medical Research Council/UKRI: MC_UU_00034/1 National Institute of General Medical Sciences of the NIH: T32GM135119
Startup funds (ALB) via the Department of Pathology and Laboratory Medicine and the School of Medicine and Public Health at the University of Wisconsin-Madison were utilized for study. ASK was supported in part by Open Philanthropy and the Life Sciences Research Foundation. JG is supported by the Wellcome Trust and Royal Society through a Sir Henry Dale Fellowship (107653/Z/15/Z) and through MRC-University of Glasgow Centre for Virus Research core support from the Medical Research Council/UKRI (MC_UU_00034/1). SM was supported by the National Institute of General Medical Sciences of the NIH training grant (T32GM135119). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
- Language
- English
- Date published
- 08/28/2024
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Internal Medicine
- Record Identifier
- 9984699524202771
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