A Gut Reaction to SIV and SHIV Infection: Lower Dysregulation of Mucosal T Cells during Acute Infection Is Associated with Greater Viral Suppression during cART
| Autor: | Cassandra Moats, Christopher W. Peterson, Thomas B. Lewis, Deborah H. Fuller, Jessica M. Osborn, Paul V. Munson, Jeremy Smedley, Kenneth C. Bagley, Hillary C. Tunggal, Megan A. O'Connor, Sandra Dross, Hans-Peter Kiem, Keith R. Jerome, James I. Mullins, Meei Li W. Huang |
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| Rok vydání: | 2021 |
| Předmět: |
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Male Sustained Virologic Response animal diseases viruses Simian Acquired Immunodeficiency Syndrome Acute infection Viremia cART medicine.disease_cause Virus Replication Microbiology T-Lymphocytes Regulatory Article Virological response Acquired immunodeficiency syndrome (AIDS) Virology medicine Animals Homeostasis Viral suppression Immunity Mucosal Intraepithelial Lymphocytes T helper 17 (Th17) mucosal dysfunction colon business.industry virus diseases Immune dysregulation Viral Load medicine.disease Macaca mulatta QR1-502 Gastrointestinal Tract AIDS models Kinetics non-human primate (NHP) Infectious Diseases Anti-Retroviral Agents SHIV SIV Immunology Acute Disease Models Animal Th17 Cells Simian Immunodeficiency Virus business T regulatory |
| Zdroj: | Viruses Volume 13 Issue 8 Viruses, Vol 13, Iss 1609, p 1609 (2021) |
| ISSN: | 1999-4915 |
| Popis: | Selection of a pre-clinical non-human primate (NHP) model is essential when evaluating therapeutic vaccine and treatment strategies for HIV. SIV and SHIV-infected NHPs exhibit a range of viral burdens, pathologies, and responses to combinatorial antiretroviral therapy (cART) regimens and the choice of the NHP model for AIDS could influence outcomes in studies investigating interventions. Previously, in rhesus macaques (RMs) we showed that maintenance of mucosal Th17/Treg homeostasis during SIV infection correlated with a better virological response to cART. Here, in RMs we compared viral kinetics and dysregulation of gut homeostasis, defined by T cell subset disruption, during highly pathogenic SIVΔB670 compared to SHIV-1157ipd3N4 infection. SHIV infection resulted in lower acute viremia and less disruption to gut CD4 T-cell homeostasis. Additionally, 24/24 SHIV-infected versus 10/19 SIV-infected animals had sustained viral suppression < 100 copies/mL of plasma after 5 months of cART. Significantly, the more profound viral suppression during cART in a subset of SIV and all SHIV-infected RMs corresponded with less gut immune dysregulation during acute SIV/SHIV infection, defined by maintenance of the Th17/Treg ratio. These results highlight significant differences in viral control during cART and gut dysregulation in NHP AIDS models and suggest that selection of a model may impact the evaluation of candidate therapeutic interventions for HIV treatment and cure strategies. |
| Databáze: | OpenAIRE |
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