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Functional cure of sivagm infection in rhesus macaques results in complete recovery of CD4 <sup>+</sup>T cells and is reverted by CD8 <sup>+</sup> cell depletion

Pandrea, I and Gaufin, T and Gautam, R and Kristoff, J and Mandell, D and Montefiori, D and Keele, BF and Ribeiro, RM and Veazey, RS and Apetrei, C (2011) Functional cure of sivagm infection in rhesus macaques results in complete recovery of CD4 <sup>+</sup>T cells and is reverted by CD8 <sup>+</sup> cell depletion. PLoS Pathogens, 7 (8). ISSN 1553-7366

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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.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Pandrea, I
Gaufin, T
Gautam, R
Kristoff, Jjak83@pitt.eduJAK83
Mandell, D
Montefiori, D
Keele, BF
Ribeiro, RM
Veazey, RS
Apetrei, Capetreic@pitt.eduAPETREIC
ContributionContributors NameEmailPitt UsernameORCID
Centers: Other Centers, Institutes, Offices, or Units > Center for Vaccine Research
Date: 1 August 2011
Date Type: Publication
Journal or Publication Title: PLoS Pathogens
Volume: 7
Number: 8
DOI or Unique Handle: 10.1371/journal.ppat.1002170
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
School of Medicine > Pathology
Refereed: Yes
ISSN: 1553-7366
MeSH Headings: Animals; Apoptosis--immunology; CD4-Positive T-Lymphocytes--immunology; CD4-Positive T-Lymphocytes--metabolism; CD4-Positive T-Lymphocytes--virology; CD8-Positive T-Lymphocytes--immunology; CD8-Positive T-Lymphocytes--metabolism; CD8-Positive T-Lymphocytes--virology; Humans; Lymphocyte Activation--immunology; Macaca mulatta; Simian Acquired Immunodeficiency Syndrome--immunology; Simian Acquired Immunodeficiency Syndrome--metabolism; Simian immunodeficiency virus--physiology; Time Factors; Virus Replication--immunology
Other ID: NLM PMC3150280
PubMed Central ID: PMC3150280
PubMed ID: 21829366
Date Deposited: 05 Sep 2012 18:15
Last Modified: 22 Jun 2021 10:55


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