HLA-C downregulation by HIV-1 adapts to host HLA genotype.

Autor: Bachtel ND; Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington DC, United States of America., Umviligihozo G; Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada., Pickering S; Department of Infectious Disease, King's College London School of Medicine, Guy's Hospital, London, United Kingdom., Mota TM; Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington DC, United States of America., Liang H; Department of Statistics and Biostatistics, George Washington University, Washington DC, United States of America., Del Prete GQ; AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, Maryland, United States of America., Chatterjee P; Cancer and Inflammation Program, HLA Immunogenetics Section, Basic Science Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, Maryland, United States of America., Lee GQ; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, United States of America., Thomas R; US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.; Henry M. Jackson Foundation, Bethesda, Maryland, United States of America., Brockman MA; Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada.; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada., Neil S; Department of Infectious Disease, King's College London School of Medicine, Guy's Hospital, London, United Kingdom., Carrington M; Cancer and Inflammation Program, HLA Immunogenetics Section, Basic Science Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, Maryland, United States of America.; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, United States of America., Bwana B; Mbarara University of Science and Technology, Mbarara, Uganda., Bangsberg DR; Mbarara University of Science and Technology, Mbarara, Uganda.; Oregon Health & Science University, Portland State University School of Public Health, Portland, Oregon, United States of America., Martin JN; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, United States of America., Kallas EG; University of Sao Paulo, Sao Paulo, Brazil., Donini CS; University of Sao Paulo, Sao Paulo, Brazil., Cerqueira NB; University of Sao Paulo, Sao Paulo, Brazil., O'Doherty UT; Departments of Medicine and Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America., Hahn BH; Departments of Medicine and Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America., Jones RB; Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington DC, United States of America., Brumme ZL; Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada.; British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada., Nixon DF; Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington DC, United States of America., Apps R; Department of Microbiology, Immunology & Tropical Medicine, The George Washington University, Washington DC, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2018 Sep 04; Vol. 14 (9), pp. e1007257. Date of Electronic Publication: 2018 Sep 04 (Print Publication: 2018).
DOI: 10.1371/journal.ppat.1007257
Abstrakt: HIV-1 can downregulate HLA-C on infected cells, using the viral protein Vpu, and the magnitude of this downregulation varies widely between primary HIV-1 variants. The selection pressures that result in viral downregulation of HLA-C in some individuals, but preservation of surface HLA-C in others are not clear. To better understand viral immune evasion targeting HLA-C, we have characterized HLA-C downregulation by a range of primary HIV-1 viruses. 128 replication competent viral isolates from 19 individuals with effective anti-retroviral therapy, show that a substantial minority of individuals harbor latent reservoir virus which strongly downregulates HLA-C. Untreated infections display no change in HLA-C downregulation during the first 6 months of infection, but variation between viral quasispecies can be detected in chronic infection. Vpu molecules cloned from plasma of 195 treatment naïve individuals in chronic infection demonstrate that downregulation of HLA-C adapts to host HLA genotype. HLA-C alleles differ in the pressure they exert for downregulation, and individuals with higher levels of HLA-C expression favor greater viral downregulation of HLA-C. Studies of primary and mutant molecules identify 5 residues in the transmembrane region of Vpu, and 4 residues in the transmembrane domain of HLA-C, which determine interactions between Vpu and HLA. The observed adaptation of Vpu-mediated downregulation to host genotype indicates that HLA-C alleles differ in likelihood of mediating a CTL response that is subverted by viral downregulation, and that preservation of HLA-C expression is favored in the absence of these responses. Finding that latent reservoir viruses can downregulate HLA-C could have implications for HIV-1 cure therapy approaches in some individuals.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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