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Determinants of pegivirus persistence, cross-species infection, and adaptation in the laboratory mouse
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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.
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Metadata
- Authors
- Nennig, K., Murthy, S., Maloney, S., Shaw, T. M., Sharobim, M., Matkovic, E., Fadiran, S., Larsen, M., Ramuta, M. D., Kim, A. S., Teijaro, J. R., Grove, J., Stremlau, M., Sharma, H., Trivedi, S., Blum, M. J., O’Connor, D. H., Hyde, J. L., Stapleton, J. T., Kapoor, A., & Bailey, A. L.
- Affiliations
- University of Wisconsin–Madison (US)
- Nationwide Children's Hospital (US)
- Scripps Research Institute (US)
- MRC University of Glasgow Centre for Virus Research (GB)
- Johns Hopkins University (US)
- University of Tennessee at Knoxville (US)
- University of Washington (US)
- University of Iowa (US)
- Corresponding author
- Bailey, Adam L.
- ORCID
- Venue
- PLOS Pathogens
- Publisher
- Public Library of Science (PLoS)
- Published
- 2024-08-28
- Volume
- 20
- Issue
- 8
- Pages
- e1012436
- ISSN
- 1553-7366 (ISSN-L)
- 1553-7374
- PMC
- PMC11355568
- OpenAlex
- W4401945901
- Cited by
- 2
- References
- 2
- Citations by year
- 2026: 1 · 2025: 1
- FWCI
- 0.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Pathogens (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Department of Pathology and Laboratory Medicine,the School of Medicine, Public Health at the University of Wisconsin–Madison
- Open Philanthropy and the Life Sciences Research Foundation
- Wellcome Trust and Royal Society (Sir Henry Dale Fellowship (107653/Z/15/Z))
- MRC-University of Glasgow Centre for Virus Research (Medical Research Council/UKRI (MC_UU_00034/1)
- National Institute of General Medical Sciences (NIH training grant (T32GM135119))
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Hepatology › Hepatitis C virus research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- Pegivirus, hepatitis G virus, viral persistence, mouse-adapted virus, cross-species infection, type I interferon, PD-1, immune evasion, viremia, immunodeficient mice, RNA virus infection, host immune response
- MeSH terms
- Persistent Infection, Animals, Humans, Mice, Inbred C57BL, Flaviviridae, Flaviviridae Infections, Mice, Rats, Immune Evasion
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