HLA Class I Downregulation by HIV-1 Variants from Subtype C Transmission Pairs

• Type of Material: Article
• Authors: Zachary Ende, Emory University; Martin J. Deymier, Emory University; Daniel T. Claiborne, Emory University; Jessica L. Prince, Emory University; Daniela C. Monaco, Emory University; William Kilembe, Zambia Emory HIV Research Project; Susan Allen, Emory University; Eric Hunter, Emory University
• Language: English
• Date: 2018-04-01
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2018 American Society for Microbiology.
• Final Published Version (URL): http://dx.doi.org/10.1128/JVI.01633-17
• Title of Journal or Parent Work: Journal of Virology
• ISSN: 0022-538X
• Volume: 92
• Issue: 7
• Start Page: e01633-17
• End Page: e01633-17
• Grant/Funding Information: E.H. is a Georgia Eminent Scholar.; M.J.D., D.D., and Z.E. were supported in part by Action Cycling Fellowships.; The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Go to: Footnotes; This study was funded by R37AI51231 and R01AI64060 (E.H.) from the National Institute of Allergy and Infectious Diseases, National Institutes of Health.; M.J.D. was supported in part by a Chateaubriand Fellowship.; This work was also supported in part by the Yerkes National Primate Research Center base grant ODP51OD11132 through the Office of Research Infrastructure Programs and by the Immunology, Clinical, and Biostatistics Cores of the Emory Center for AIDS Research, supported by grant P30AI050409 from the National Institute of Allergy and Infectious Diseases.
• Keywords: MAJOR DETERMINANT; HUMAN-IMMUNODEFICIENCY-VIRUS; human leukocyte antigen class I; COMPLEX CLASS-I; Vpu; Life Sciences & Biomedicine; HUMAN-LEUKOCYTE ANTIGEN; Nef; MHC-I; NK cells; CELL-SURFACE; ZAMBIAN COUPLES; DISEASE PROGRESSION; HLA; transmitted/founder virus; HIV-1; TRANSMITTED FOUNDER HIV-1; quasispecies; natural killer cells; Science & Technology; Virology; HETEROSEXUAL TRANSMISSION; human immunodeficiency virus
• Research Categories: Biology, Virology; Biology, Microbiology; Health Sciences, Immunology

Abstract

HIV-1 downregulates human leukocyte antigen A (HLA-A) and HLA-B from the surface of infected cells primarily to evade CD8 T cell recognition. HLA-C was thought to remain on the cell surface and bind inhibitory killer immunoglobulin-like receptors, preventing natural killer (NK) cell-mediated suppression. However, a recent study found HIV-1 primary viruses have the capacity to downregulate HLA-C. The goal of this study was to assess the heterogeneity of HLA-A, HLA-B, and HLA-C downregulation among full-length primary viruses from six chronically infected and six newly infected individuals from transmission pairs and to determine whether transmitted/founder variants exhibit common HLA class I downregulation characteristics. We measured HLA-A, HLA-B, HLA-C, and total HLA class I downregulation by flow cytometry of primary CD4 T cells infected with 40 infectious molecular clones. Primary viruses mediated a range of HLA class I downregulation capacities (1.3- to 6.1-fold) which could differ significantly between transmission pairs. Downregulation of HLA-C surface expression on infected cells correlated with susceptibility to in vitro NK cell suppression of virus release. Despite this, transmitted/founder variants did not share a downregulation signature and instead were more similar to the quasispecies of matched donor partners. These data indicate that a range of viral abilities to downregulate HLA-A, HLA-B, and HLA-C exist within and between individuals that can have functional consequences on immune recognition.