Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Aug;69(8-9):511-519.
doi: 10.1007/s00251-017-0997-3. Epub 2017 Jul 10.

The role of MHC class I gene products in SIV infection of macaques

Zachary A Silver  1   2 , David I Watkins  3
Affiliations
Review

The role of MHC class I gene products in SIV infection of macaques

Zachary A Silver et al. Immunogenetics. 2017 Aug.

Abstract

Human immunodeficiency virus (HIV) remains among the most significant public health threats worldwide. Despite three decades of research following the discovery of HIV, a preventive vaccine remains elusive. The study of HIV elite controllers has been crucial to elaborate the genetic and immunologic determinants that underlie control of HIV replication. Coordinated studies of elite control in humans have, however, been limited by variability among infecting viral strains, host genotype, and the uncertainty of the timing and route of infection. In this review, we discuss the role of nonhuman primate (NHP) models for the elucidation of the immunologic correlates that underlie control of AIDS virus replication. We discuss the importance of major histocompatibility complex class I (MHC-I) alleles in activating CD8+ T-cell populations that promote control of both HIV and simian immunodeficiency virus (SIV) replication. Provocatively, we make the argument that T-cell subsets recognizing the HIV/SIV viral infectivity factor (Vif) protein may be crucial for control of viral replication. We hope that this review demonstrates how an in-depth understanding of the MHC-I gene products associated with elite control of HIV/SIV, and the epitopes that they present, can provide researchers with a glimpse into the protective immune responses that underlie AIDS nonprogression.

Keywords: Cytotoxic T lymphocyte (CTL); Human immunodeficiency virus (HIV); Major histocompatibility complex (MHC); Nonhuman primate (NHP) model for AIDS; Simian immunodeficiency virus (SIV).

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Relationship between APOBEC3G, Vif, MHC presentation, and CTL responses. a Proteasomal degradation of the Vif/A3G complex limits incorporation of A3G into progeny virions, thereby preventing hypermutation during subsequent cellular infection. This proteasomal degradation may lead to increased presentation of Vif epitopes in the context of MHC-I gene products and provide a target for Vif-specific CTLs. Vif-specific T-cell responses may therefore be key for control of HIV/SIV by targeting cells that evade the activity of the A3G restriction factor. b In the absence of Vif, A3G is incorporated into progeny virions. Upon infection of subsequent cells, A3G causes mutations during reverse transcription of viral RNA that result in replication-incompetent virus
Fig. 2
Fig. 2
HIV and SIV Vif are targeted for presentation by MHC-I gene products. The major function of HIV/SIV Vif is to prevent incorporation of A3G into the capsid of progeny virus by targeting the Vif/A3G complex to the proteasome. In so doing, the AIDS virus is able to prevent hypermutation of its progeny virus upon infection of a subsequent cell. This Vif amino acid alignment depicts the SIV and HIV Vif minimal optimal epitopes and the MHC-I gene products that present them. In addition, we show the extent of overlap between the Vif minimal optimal epitopes and known functional domains of Vif. The HIV Vif HCCH motif (amino acids shown in red) binds to Cul5. References: SIVmac239 epitopes (see Table 1), HIV-1 epitopes (Llano et al. 2013), Elo B/C binding (Stanley et al. 2008), Cul5 binding (Dang et al. ; Luo et al. ; Stanley et al. 2008), A3G binding (Chen et al. ; Dang et al. ; Russell and Pathak 2007), A3F binding (Dang et al. ; He et al. ; Russell and Pathak 2007), A3G and A3F binding (Dang et al. ; He et al. ; Pery et al. 2009)
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Addo MM, Altfeld M, Brainard DM, Rathod A, Piechocka-Trocha A, Fideli U, Mulenga J, Shutes E, Alvino DM, Hunter E, Allen SA, Walker BD. Lack of detectable HIV-1-specific CD8(+) T cell responses in Zambian HIV-1-exposed seronegative partners of HIV-1-positive individuals. J Infect Dis. 2011;203:258–262. doi: 10.1093/infdis/jiq028. - DOI - PMC - PubMed
    1. Ahlers JD, Belyakov IM. Lessons learned from natural infection: focusing on the design of protective T cell vaccines for HIV/AIDS. Trends Immunol. 2010;31:120–130. doi: 10.1016/j.it.2009.12.003. - DOI - PubMed
    1. Allen TM, Sidney J, del Guercio MF, Glickman RL, Lensmeyer GL, Wiebe DA, DeMars R, Pauza CD, Johnson RP, Sette A, Watkins DI. Characterization of the peptide binding motif of a rhesus MHC class I molecule (Mamu-A*01) that binds an immunodominant CTL epitope from simian immunodeficiency virus. J Immunol. 1998;160:6062–6071. - PubMed
    1. Allen TM, Mothe BR, Sidney J, Jing P, Dzuris JL, Liebl ME, Vogel TU, O’Connor DH, Wang X, Wussow MC, Thomson JA, Altman JD, Watkins DI, Sette A. CD8(+) lymphocytes from simian immunodeficiency virus-infected rhesus macaques recognize 14 different epitopes bound by the major histocompatibility complex class I molecule mamu-A*01: implications for vaccine design and testing. J Virol. 2001;75:738–749. doi: 10.1128/JVI.75.2.738-749.2001. - DOI - PMC - PubMed
    1. Allers K, Hutter G, Hofmann J, Loddenkemper C, Rieger K, Thiel E, Schneider T. Evidence for the cure of HIV infection by CCR5Delta32/Delta32 stem cell transplantation. Blood. 2011;117:2791–2799. doi: 10.1182/blood-2010-09-309591. - DOI - PubMed

LinkOut - more resources