PLoS Pathogens (May 2019)

Limited HIV-2 reservoirs in central-memory CD4 T-cells associated to CXCR6 co-receptor expression in attenuated HIV-2 infection.

  • Assia Samri,
  • Charlotte Charpentier,
  • Mariama Sadjo Diallo,
  • Mélanie Bertine,
  • Sophie Even,
  • Véronique Morin,
  • Anne Oudin,
  • Christophe Parizot,
  • Gilles Collin,
  • Anne Hosmalin,
  • Rémi Cheynier,
  • Rodolphe Thiébaut,
  • Sophie Matheron,
  • Fideline Collin,
  • Rima Zoorob,
  • Françoise Brun-Vézinet,
  • Brigitte Autran,
  • ANRS CO5 IMMUNOVIR-2 Study Group

DOI
https://doi.org/10.1371/journal.ppat.1007758
Journal volume & issue
Vol. 15, no. 5
p. e1007758

Abstract

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The low pathogenicity and replicative potential of HIV-2 are still poorly understood. We investigated whether HIV-2 reservoirs might follow the peculiar distribution reported in models of attenuated HIV-1/SIV infections, i.e. limited infection of central-memory CD4 T lymphocytes (TCM). Antiretroviral-naive HIV-2 infected individuals from the ANRS-CO5 (12 non-progressors, 2 progressors) were prospectively included. Peripheral blood mononuclear cells (PBMCs) were sorted into monocytes and resting CD4 T-cell subsets (naive [TN], central- [TCM], transitional- [TTM] and effector-memory [TEM]). Reactivation of HIV-2 was tested in 30-day cultures of CD8-depleted PBMCs. HIV-2 DNA was quantified by real-time PCR. Cell surface markers, co-receptors and restriction factors were analyzed by flow-cytometry and multiplex transcriptomic study. HIV-2 DNA was undetectable in monocytes from all individuals and was quantifiable in TTM from 4 individuals (median: 2.25 log10 copies/106 cells [IQR: 1.99-2.94]) but in TCM from only 1 individual (1.75 log10 copies/106 cells). HIV-2 DNA levels in PBMCs (median: 1.94 log10 copies/106 PBMC [IQR = 1.53-2.13]) positively correlated with those in TTM (r = 0.66, p = 0.01) but not TCM. HIV-2 reactivation was observed in the cells from only 3 individuals. The CCR5 co-receptor was distributed similarly in cell populations from individuals and donors. TCM had a lower expression of CXCR6 transcripts (p = 0.002) than TTM confirmed by FACS analysis, and a higher expression of TRIM5 transcripts (p = 0.004). Thus the low HIV-2 reservoirs differ from HIV-1 reservoirs by the lack of monocytic infection and a limited infection of TCM associated to a lower expression of a potential alternative HIV-2 co-receptor, CXCR6 and a higher expression of a restriction factor, TRIM5. These findings shed new light on the low pathogenicity of HIV-2 infection suggesting mechanisms close to those reported in other models of attenuated HIV/SIV infection models.