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
Megan A. O’Connor,
Paul V. Munson,
Sandra E. Dross,
Hillary C. Tunggal,
Thomas B. Lewis,
Jessica Osborn,
Christopher W. Peterson,
Meei-Li W. Huang,
Cassandra Moats,
Jeremy Smedley,
Keith R. Jerome,
Hans-Peter Kiem,
Kenneth C. Bagley,
James I. Mullins,
Deborah Heydenburg Fuller
Affiliations
Megan A. O’Connor
Department of Microbiology, University of Washington, 750 Republican St., Seattle, WA 98109, USA
Paul V. Munson
Department of Microbiology, University of Washington, 750 Republican St., Seattle, WA 98109, USA
Sandra E. Dross
Department of Microbiology, University of Washington, 750 Republican St., Seattle, WA 98109, USA
Hillary C. Tunggal
Department of Microbiology, University of Washington, 750 Republican St., Seattle, WA 98109, USA
Thomas B. Lewis
Department of Microbiology, University of Washington, 750 Republican St., Seattle, WA 98109, USA
Jessica Osborn
Department of Microbiology, University of Washington, 750 Republican St., Seattle, WA 98109, USA
Christopher W. Peterson
Stem Cell and Gene Therapy Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109, USA
Meei-Li W. Huang
Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA
Cassandra Moats
Washington National Primate Research Center, 1705 NE Pacific Street, Seattle, WA 98195, USA
Jeremy Smedley
Washington National Primate Research Center, 1705 NE Pacific Street, Seattle, WA 98195, USA
Keith R. Jerome
Stem Cell and Gene Therapy Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109, USA
Hans-Peter Kiem
Stem Cell and Gene Therapy Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109, USA
Kenneth C. Bagley
Profectus Biosciences Inc., 6411 Beckley Street, Baltimore, MD 21224, USA
James I. Mullins
Department of Microbiology, University of Washington, 750 Republican St., Seattle, WA 98109, USA
Deborah Heydenburg Fuller
Department of Microbiology, University of Washington, 750 Republican St., Seattle, WA 98109, USA
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.
