Functional Cure of SIVagm Infection in Rhesus Macaques Results in Complete Recovery of CD4⁺ T Cells and Is Reverted by CD8⁺ Cell Depletion

Journal Article · Thu Aug 04 00:00:00 EDT 2011 · PLoS Pathogens

DOI:https://doi.org/10.1371/journal.ppat.1002170· OSTI ID:1627900

Pandrea, Ivona ^[1]; Gaufin, Thaidra ^[2]; Gautam, Rajeev ^[2]; Kristoff, Jan ^[3]; Mandell, Daniel ^[2]; Montefiori, David ^[4]; Keele, Brandon F. ^[5]; Ribeiro, Ruy M. ^[6]; Veazey, Ronald S. ^[2]; Apetrei, Cristian ^[7]

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1. Tulane National Primate Research Center, Covington, LA (United States); University of Pittsburgh, PA (United States); DOE/OSTI
2. Tulane National Primate Research Center, Covington, LA (United States)
3. University of Pittsburgh, PA (United States)
4. Duke University, Durham, NC (United States)
5. SAIC Frederick, Inc, Frederick, MD (United States)
6. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
7. University of Pittsburgh, PA (United States); Tulane National Primate Research Center, Covington, LA (United States)

Understanding the mechanism of infection control in elite controllers (EC) may shed light on the correlates of control of disease progression in HIV infection. However, limitations have prevented a clear understanding of the mechanisms of elite controlled infection, as these studies can only be performed at randomly selected late time points in infection, after control is achieved, and the access to tissues is limited. We report that SIVagm infection is elite-controlled in rhesus macaques (RMs) and therefore can be used as an animal model for EC HIV infection. A robust acute infection, with high levels of viral replication and dramatic mucosal CD4⁺ T cell depletion, similar to pathogenic HIV-1/SIV infections of humans and RMs, was followed by complete and durable control of SIVagm replication, defined as: undetectable VLs in blood and tissues beginning 72 to 90 days postinoculation (pi) and continuing at least 4 years; seroreversion; progressive recovery of mucosal CD4⁺ T cells, with complete recovery by 4 years pi; normal levels of T cell immune activation, proliferation, and apoptosis; and no disease progression. This ‘‘functional cure’’ of SIVagm infection in RMs could be reverted after 4 years of control of infection by depleting CD8 cells, which resulted in transient rebounds of VLs, thus suggesting that control may be at least in part immune mediated. Viral control was independent of MHC, partial APOBEC restriction was not involved in SIVagm control in RMs and Trim5 genotypes did not impact viral replication. This new animal model of EC lentiviral infection, in which complete control can be predicted in all cases, permits research on the early events of infection in blood and tissues, before the defining characteristics of EC are evident and when host factors are actively driving the infection towards the EC status.

• Research Organization: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
• Sponsoring Organization: American Foundation for AIDS Research (AMFAR); National Institutes of Health (NIH); Tulane Research Enhancement Fund; USDOE Office of Science (SC), Biological and Environmental Research (BER)
• Grant/Contract Number: AC52-06NA25396
• OSTI ID: 1627900
• Journal Information: PLoS Pathogens, Journal Name: PLoS Pathogens Journal Issue: 8 Vol. 7; ISSN 1553-7374
• Publisher: Public Library of Science
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
SIV
T cells
animal models of infection
apoptosis
gastrointestinal tract
immune activation
infectious disease control
viral replication