Control of HIV-1 Pathogenesis in Viremic Nonprogressors Is Independent of Gag-Specific Cytotoxic T Lymphocyte Responses.

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  • Additional Information
    • Source:
      Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0113724 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1098-5514 (Electronic) Linking ISSN: 0022538X NLM ISO Abbreviation: J Virol Subsets: MEDLINE
    • Publication Information:
      Publication: Washington Dc : American Society For Microbiology
      Original Publication: Baltimore, American Society for Microbiology.
    • Subject Terms:
      CD4-Positive T-Lymphocytes/*virology ; HIV Infections/*pathology ; HIV-1/*immunology ; T-Lymphocytes, Cytotoxic/*immunology ; Viremia/*immunology ; gag Gene Products, Human Immunodeficiency Virus/*immunology; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes/immunology ; HIV Infections/blood ; HIV Infections/immunology ; HIV Infections/virology ; HIV-1/pathogenicity ; Humans ; Viral Load ; Viremia/virology ; Virus Replication/immunology ; gag Gene Products, Human Immunodeficiency Virus/genetics
    • Abstract:
      Viremic nonprogressors (VNPs) constitute a very scarce group of untreated human immunodeficiency virus type 1 (HIV-1)-infected individuals who maintain stable CD4 + T cell counts despite high levels of HIV-1 replication. The specific factors associated with this atypical control of the HIV infection have been poorly described. Since specific T cell responses seem to be one of the main causes of HIV-1 control in elite controllers, we studied whether HIV-1 Gag-specific cytotoxic T lymphocyte (CTL) responses could also modulate disease control in VNPs. We characterized the immune responses from four VNPs compared to those of five standard progressors (SPs) during the first years of HIV-1 infection. We observed no differences in the breadth and frequency of Gag-specific cellular responses. Furthermore, we obtained 217 HIV-1 Gag clonal sequences in which the viral variability of Gag increased over 3 years of infection for synonymous and nonsynonymous mutations in both VNPs and SPs. VNPs evolution rates in gag were comparable to SPs. This observation is in line with a similar accumulation of CTL putative escape mutations in Gag epitopes targeted by CTL responses. Altogether, the absence of viral pathogenesis in VNP individuals seems to be independent of HIV-Gag-specific CTL responses. This novel information guides to the study of alternative mechanism of HIV-1 pathogenesis control. IMPORTANCE Control of HIV infection has been widely studied in elite controllers or long-term nonprogressor models. However, there is a less-known group of individuals, termed viremic nonprogressors (VNPs), who maintain stable CD4 + T cell counts despite high plasma viremia. The mechanisms involved in this remarkable control of HIV-1 pathogenesis clearly have implications for the development of new drugs and vaccines. We show here for the first time that VNPs have immune responses and HIV-gag evolution similar to those of standard progressors. Remarkably, we demonstrate that the mechanism of pathogenesis control in these individuals differs from some elite controllers that are reported to have improved immune control. This is noteworthy since it opens the door to new, as-yet-unknown mechanisms for HIV control. Our novel results advance the understanding of mechanisms involved in viremic nonprogression and suggest that there are alternative mechanisms to the adaptive immune responses for an effective control of viral pathogenesis.
      (Copyright © 2018 Salgado et al.)
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    • Contributed Indexing:
      Keywords: CTL response; HIV-1; progression; viral pathogenesis; viremic nonprogressors
    • Accession Number:
      0 (gag Gene Products, Human Immunodeficiency Virus)
    • Publication Date:
      Date Created: 20180330 Date Completed: 20180619 Latest Revision: 20181114
    • Publication Date:
      20221213
    • Accession Number:
      PMC5974496
    • Accession Number:
      10.1128/JVI.00346-18
    • Accession Number:
      29593044