title: CCR5-restricted HIV type 2 variants from long-term aviremic individuals are less sensitive to inhibition by beta-chemokines than low pathogenic HIV type 1 variants.
abstract: Many HIV-2-infected individuals maintain low, often undetectable, viral loads for prolonged periods. Virus and/or host factors that contribute to this high level of virus control are largely unknown. Previously we demonstrated that HIV-2 variants from long-term aviremic individuals have relatively low replication kinetics in vitro in comparison to HIV-1 variants. We hypothesized that the relatively low replication rates of HIV-2 in vitro as well as the high level of virus control in vivo might be explained by HIV-2 replication being more sensitive to inhibitory host factors like beta-chemokines or other CD8+ T cell-derived factors than HIV-1 replication. To test this we determined the effect of exogenously added beta-chemokines and healthy donor CD8+ T cells on the in vitro virus production of HIV-2 and HIV-1 variants from long-term nonprogressors (LTNPs). Contrary to expectations, HIV-2 replication was inhibited less efficiently by RANTES and MIP-1alpha than HIV-1 replication. CD8+ T cells from 8 of 12 healthy donors reduced HIV replication minimally 2-fold. Interestingly, cells from five of these donors inhibited HIV-1 but hardly affected HIV-2 replication, while the reverse was observed for cells from one donor. For HIV-1, but not HIV-2, the magnitude of the antiviral effect of CD8+ T cells correlated with their effect on RANTES levels in culture supernatants. Our findings indicate that RANTES is a more important factor of CD8+ T cell-associated anti-HIV-1 activity than it is of HIV-2 activity and that the benign clinical course of HIV-2 infection is not due to enhanced beta-chemokine sensitivity of HIV-2 variants.
authors.affiliation: Department of Virology, Erasmus Medical Center (Erasmus MC), Rotterdam, The Netherlands. hetty_blaak@rivm.nl
authors.forename: Hetty
authors.initials: H
authors.lastname: Blaak
authors.forename: Patrick H M
authors.initials: PH
authors.lastname: Boers
authors.forename: Marchina E
authors.initials: ME
authors.lastname: van der Ende
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000276:immunology*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D015498:HIV-2 / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D019562:Viral Load; D014779:Virus Replication / Q000276:immunology
chemical_list: D019742:Chemokines, CC; D012194:RNA-Directed DNA Polymerase