Pegivirus avoids immune recognition but does not attenuate acute-phase disease in a macaque model of HIV infection

• Published in: PLoS pathogens Vol. 13; no. 10; p. e1006692
• Main Authors: Bailey, Adam L, Buechler, Connor R, Matson, Daniel R, Peterson, Eric J, Brunner, Kevin G, Mohns, Mariel S, Breitbach, Meghan, Stewart, Laurel M, Ericsen, Adam J, Newman, Christina M, Koenig, Michelle R, Mohr, Emma, Tan, John, Capuano, 3rd, Saverio, Simmons, Heather A, Yang, David T, O'Connor, David H
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.10.2017; Public Library of Science (PLoS)
• Subjects: Adaptive immunity; Animals; Antigens; Biology and life sciences; CD4 antigen; Cell activation; Chronic infection; Coinfection - immunology; Coinfection - virology; Disease Models, Animal; Flaviviridae Infections - immunology; Flaviviridae Infections - virology; Flaviviruses; Funding; GB virus C; Health aspects; Hepatitis; HIV; HIV infections; HIV patients; Human immunodeficiency virus; Human populations; Immune response; Immune system; Immunology; Infections; Laboratories; Lymphocytes; Lymphocytes T; Macaca fascicularis; Macaques; Medicine; Medicine and Health Sciences; Monkeys & apes; Pathogenesis; Pathology; Physiological aspects; Research and Analysis Methods; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Acquired Immunodeficiency Syndrome - virology; Simian Immunodeficiency Virus; T cell receptors; Viral infections; Virology; Viruses; United States > US; Wisconsin
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1006692

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, immune activation, or adaptive immune responses-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.