Pegivirus avoids immune recognition but does not attenuate acute-phase disease in a macaque model of HIV infection
Year: 2017
Type: article
Abstract: Human pegivirus (HPgV) protects HIV+ people from HIV-associated disease, but the mechanism of this protective effect remains poorly understood. We sequentially infected cynomolgus macaques with simian pegivirus (SPgV) and simian immunodeficiency virus (SIV) to model HIV+HPgV co-infection. SPgV had no effect on acute-phase SIV pathogenesis – as measured by SIV viral load, CD4+ T cell destruction, and immune activation – suggesting that HPgV’s protective effect is exerted primarily during the chronic phase of HIV infection. We also examined the immune response to SPgV in unprecedented detail, and found that this virus elicits virtually no activation of the immune system despite persistently high titers in the blood over long periods of time. Overall, this study expands our understanding of the pegiviruses – an understudied group of viruses with a high prevalence in the global human population – and suggests that the protective effect observed in HIV+HPgV co-infected people occurs primarily during the chronic phase of HIV infection. One Sentence Summary Pegivirus avoids immune recognition but does not attenuate acute-phase disease in a macaque model of HIV infection. Short Title Pegivirus and AIDS-virus co-infection Accessible Summary People infected with HIV live longer, healthier lives when they are co-infected with the human pegivirus (HPgV) – an understudied virus with a high prevalence in the global human population. To better understand how HPgV protects people with HIV from HIV-associated disease, we infected macaques with simian versions of these two viruses (SPgV and SIV). We found that SPgV had no impact on the incidence of SIV-associated disease early during the course of SIV infection – a time when SIV and HIV are known to cause irreversible damage to the immune system. Oddly, we found that the immune system did not recognize SPgV; a finding that warrants further investigation. Overall, this study greatly expands on our understanding of the pegiviruses and their interaction with the immune system.
Source: PLoS Pathogens
Authors: Adam L. Bailey, Connor R. Buechler, Daniel R. Matson, Eric J. Peterson, Kevin G. Brunner, Mariel S. Mohns, Meghan Breitbach, Laurel M. Stewart, Adam J. Ericsen, Christina M. Newman, Michelle R. Koenig, Emma Mohr, John Tan, Saverio Capuano, Heather A. Simmons, David T. Yang, David H. O’Connor
Institution: University of Wisconsin–Madison
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: University of Wisconsin-Madison, University of Wisconsin Carbone Cancer Center, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Center for Research Resources, Office of Research Infrastructure Programs, National Institutes of Health
Awards: G1382718699, G1712026730, G228736896, G2503872370, EXTRAMURAL RESEARCH FACILITIES CONSTRUCTION, G3751251686, G4004214011, EXTRAMURAL REGIONAL FACILITIES CONSTRUCTION, G5813506420, GBV-C-mediated protection from AIDS in humans and GBV-C/SIV co-infected macaques, Virology Training Grant, Integrated Training For Physician-Scientists, High-throughput identification of common CD8+ T cell responses to SIV and M. tuberculosis in rhesus macaques, G9000352744, Wisconsin National Primate Research Center Support, UW Comprehensive Cancer Center Support
OpenAlex ID: W2949555575