Modulation of CCR5 expression and R5 HIV-1 infection in primary macrophages exposed to sera from HESN, LTNP, and chronically HIV-1 infected people with or without natural antibodies to CCR5

Virus Res. 2024 Dec:350:199506. doi: 10.1016/j.virusres.2024.199506. Epub 2024 Dec 9.

Abstract

CCR5 is the main co-receptor for HIV-1 cell entry and it plays key roles in HIV-1 mucosal transmission. Natural anti-CCR5 antibodies were found in HIV-1-exposed seronegative and long-term non-progressor subjects, suggesting a role in controlling viral replication in vivo. We assessed the effect of sera containing or not natural anti-CCR5 antibodies, on membrane CCR5 level and HIV-1 infection in primary macrophages. Sera modulated CCR5 expression with a trend dependent on the donor/serum tested but independent on the presence or absence of anti-CCR5 antibodies. All sera strongly reduced HIV-1 DNA in all donor's macrophages and no correlation was observed between CCR5 and viral DNA levels. These results suggest that CCR5 expression level is not a major determinant of macrophage infection and that the observed modulation of CCR5 and HIV-1 DNA might depend on factors other than CCR5-reactive antibodies present in sera and/or intrinsic to the donors on which sera were tested.

Keywords: HIV-1; Natural anti-CCR5 antibody; Primary macrophage.

MeSH terms

  • Adult
  • Cells, Cultured
  • Female
  • HIV Antibodies / blood
  • HIV Antibodies / immunology
  • HIV Infections* / immunology
  • HIV Infections* / virology
  • HIV-1* / genetics
  • HIV-1* / immunology
  • Humans
  • Macrophages* / immunology
  • Macrophages* / virology
  • Male
  • Middle Aged
  • Receptors, CCR5* / genetics
  • Receptors, CCR5* / immunology

Substances

  • Receptors, CCR5
  • CCR5 protein, human
  • HIV Antibodies