T Cells Target APOBEC3 Proteins in Human Immunodeficiency Virus Type 1-Infected Humans and Simian Immunodeficiency Virus-Infected Indian Rhesus Macaques

Champiat, Stéphane; Garrison, Keith; Raposo, Rui André Saraiva; Burwitz, Benjamin J.; Reed, Jason S.; Tandon, Ravi; York, Vanessa A.; Newman, Laura P.; Nimityongskul, Francesca A.; Wilson, Nancy A.; Almeida, Rafael Ribeiro; Martin, Jeffrey N.; Deeks, Steven G.; Rosenberg, Michael; Wiznia, Andrew; Spotts, Gerald; Pilcher, Christopher D.; Hecht, Frederick M.; Ostrowski, Mario; Sacha, Jonah B.; Nixon, Douglas F.

doi:10.1128/jvi.00579-12

Cited by 4 publications

(4 citation statements)

References 36 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two different ways in which higher cellular A3G may augment CTL activity have been demonstrated experimentally to date, via either enhanced recognition of HIV-specific antigens encoded by replication-defective, hypermutated proviruses [13] or increased recognition of A3G itself presented on the cell surface (because of greater proteosomal degradation of A3G in Vif-positive HIV-infected lymphocytes) [14]. However, neither report evaluated cells expressing HLA B57 or B27, so relevance for the subjects studied here is uncertain [13], [14]. A3G also has been reported to enhance recognition of HIV-infected T lymphocytes by natural killer (NK) cells [33], although not yet documented ex vivo in the one study of this in controllers to date [34].…”

Section: Discussionmentioning

confidence: 99%

Lower HIV Provirus Levels Are Associated with More APOBEC3G Protein in Blood Resting Memory CD4+ T Lymphocytes of Controllers In Vivo

et al. 2013

View full text Add to dashboard Cite

Immunodeficiency does not progress for prolonged periods in some HLA B57- and/or B27-positive subjects with human immunodeficiency virus type 1 (HIV) infection, even in the absence of antiretroviral therapy (ART). These “controllers” have fewer HIV provirus-containing peripheral blood mononuclear cells than “non-controller” subjects, but lymphocytes that harbor latent proviruses were not specifically examined in studies to date. Provirus levels in resting memory cells that can serve as latent reservoirs of HIV in blood were compared here between controllers and ART-suppressed non-controllers. APOBEC3G (A3G), a cellular factor that blocks provirus formation at multiple steps if not antagonized by HIV virion infectivity factor (Vif), was also studied. HLA-linked HIV control was associated with less provirus and more A3G protein in resting CD4+ T central memory (Tcm) and effector memory (Tem) lymphocytes (provirus: p = 0.01 for Tcm and p = 0.02 for Tem; A3G: p = 0.02 for Tcm and p = 0.02 for Tem). Resting memory T cells with the highest A3G protein levels (>0.5 RLU per unit of actin) had the lowest levels of provirus (<1,000 copies of DNA per million cells) in vivo (p = 0.03, Fisher's exact test). Using two different experimental approaches, Vif-positive viruses with more A3G were found to have decreased virion infectivity ex vivo. These results raise the hypothesis that HIV control is associated with increased cellular A3G that may be packaged into Vif-positive virions to add that mode of inhibition of provirus formation to previously described adaptive immune mechanisms for HIV control.

show abstract

Section: Discussionmentioning

confidence: 99%

Lower HIV Provirus Levels Are Associated with More APOBEC3G Protein in Blood Resting Memory CD4+ T Lymphocytes of Controllers In Vivo

et al. 2013

View full text Add to dashboard Cite

show abstract

“…ELISPOT screening was carried out as previous described [ 26 ] using 15-mer peptides (with 11 amino acid overlap) spanning the entire SERV-K1 Env open reading frame or the entire SIVmac239 proteome. Intracellular cytokine staining assays were carried out as previously described [ 21 , 26 ]. Positive responses shown were confirmed using peptides synthesized by three independent sources.…”

Section: Methodsmentioning

confidence: 99%

Identification and spontaneous immune targeting of an endogenous retrovirus K envelope protein in the Indian rhesus macaque model of human disease

León

Wallace

et al. 2016

Retrovirology

Self Cite

View full text Add to dashboard Cite

BackgroundEndogenous retroviruses (ERVs) are remnants of ancient retroviral infections that have invaded the germ line of both humans and non-human primates. Most ERVs are functionally crippled by deletions, mutations, and hypermethylation, leading to the view that they are inert genomic fossils. However, some ERVs can produce mRNA transcripts, functional viral proteins, and even non-infectious virus particles during certain developmental and pathological processes. While there have been reports of ERV-specific immunity associated with ERV activity in humans, adaptive immune responses to ERV-encoded gene products remain poorly defined and have not been investigated in the physiologically relevant non-human primate model of human disease.FindingsHere, we identified the rhesus macaque equivalent of the biologically active human ERV-K (HML-2), simian ERV-K (SERV-K1), which retains intact open reading frames for both Gag and Env on chromosome 12 in the macaque genome. From macaque cells we isolated a spliced mRNA product encoding SERV-K1 Env, which possesses all the structural features of a canonical, functional retroviral Envelope protein. Furthermore, we identified rare, but robust T cell responses as well as frequent antibody responses targeting SERV-K1 Env in rhesus macaques.ConclusionsThese data demonstrate that SERV-K1 retains biological activity sufficient to induce cellular and humoral immune responses in rhesus macaques. As ERV-K is the youngest and most active ERV family in the human genome, the identification and characterization of the simian orthologue in rhesus macaques provides a highly relevant animal model in which to study the role of ERV-K in developmental and disease states.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-016-0238-0) contains supplementary material, which is available to authorized users.

show abstract

“…Remarkably, in HIV-1-infected cells, following interactions with Vif, A3G is poly-ubiquitinated and hence constitute itself a substrate for UPS-mediated degradation (38), providing as a consequence epitopes for MHC-I presentation. Indeed, A3G (and A3F)-specific CTL responses have been observed in both HIV-1-infected patients and SIV-infected rhesus macaques (169). Therefore, presentation of A3G-derived epitopes might also be a hallmark of HIV-1-infected cells targeted by the adaptive immune response.…”

Section: Restriction Factors and Protein Degradation Pathwaysmentioning

confidence: 99%

Restriction Factors: From Intrinsic Viral Restriction to Shaping Cellular Immunity Against HIV-1

et al. 2018

View full text Add to dashboard Cite

Antiviral restriction factors are host cellular proteins that constitute a first line of defense blocking viral replication and propagation. In addition to interfering at critical steps of the viral replication cycle, some restriction factors also act as innate sensors triggering innate responses against infections. Accumulating evidence suggests an additional role for restriction factors in promoting antiviral cellular immunity to combat viruses. Here, we review the recent progress in our understanding on how restriction factors, particularly APOBEC3G, SAMHD1, Tetherin, and TRIM5α have the cell-autonomous potential to induce cellular resistance against HIV-1 while promoting antiviral innate and adaptive immune responses. Also, we provide an overview of how these restriction factors may connect with protein degradation pathways to modulate anti-HIV-1 cellular immune responses, and we summarize the potential of restriction factors-based therapeutics. This review brings a global perspective on the influence of restrictions factors in intrinsic, innate, and also adaptive antiviral immunity opening up novel research avenues for therapeutic strategies in the fields of drug discovery, gene therapy, and vaccines to control viral infections.

show abstract

T Cells Target APOBEC3 Proteins in Human Immunodeficiency Virus Type 1-Infected Humans and Simian Immunodeficiency Virus-Infected Indian Rhesus Macaques

Cited by 4 publications

References 36 publications

Lower HIV Provirus Levels Are Associated with More APOBEC3G Protein in Blood Resting Memory CD4+ T Lymphocytes of Controllers In Vivo

Lower HIV Provirus Levels Are Associated with More APOBEC3G Protein in Blood Resting Memory CD4+ T Lymphocytes of Controllers In Vivo

Identification and spontaneous immune targeting of an endogenous retrovirus K envelope protein in the Indian rhesus macaque model of human disease

Restriction Factors: From Intrinsic Viral Restriction to Shaping Cellular Immunity Against HIV-1

Contact Info

Product

Resources

About