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

• Published in: PLoS pathogens Vol. 15; no. 5; p. e1007758
• Main Authors: Samri, Assia, Charpentier, Charlotte, Diallo, Mariama Sadjo, Bertine, Mélanie, Even, Sophie, Morin, Véronique, Oudin, Anne, Parizot, Christophe, Collin, Gilles, Hosmalin, Anne, Cheynier, Rémi, Thiébaut, Rodolphe, Matheron, Sophie, Collin, Fideline, Zoorob, Rima, Brun-Vézinet, Françoise, Autran, Brigitte
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.05.2019; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Activation; Adaptive immunology; Adult; Aged; AIDS; Antiretroviral agents; Attenuation; Biology and Life Sciences; Carrier Proteins - genetics; Carrier Proteins - metabolism; Case-Control Studies; CCR5 protein; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - virology; CD8 antigen; Cell surface; Cells, Cultured; Cytometry; Deoxyribonucleic acid; DNA; Female; Flow cytometry; Funding; Gene expression; Genetic aspects; Hepatitis; HIV; HIV infections; HIV Infections - immunology; HIV Infections - metabolism; HIV Infections - virology; HIV tests; HIV-2 - genetics; HIV-2 - immunology; Human health and pathology; Human immunodeficiency virus; Humans; Immunologic Memory - immunology; Immunological memory; Immunology; Infection; Infections; Infectious diseases; Leukocytes (mononuclear); Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - virology; Life Sciences; Lymphocytes; Lymphocytes T; Male; Medicine and Health Sciences; Memory cells; Microbiology and Parasitology; Middle Aged; Monocytes; Pathogenicity; Pathogens; Peripheral blood mononuclear cells; Receptors; Receptors, CXCR6 - genetics; Receptors, CXCR6 - metabolism; Simian immunodeficiency virus; Supervision; Surface markers; T cells; Transcriptome; Virology; France; Africa
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1007758

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.