CXCR4 mediates entry and productive infection of syncytia-inducing (X4) HIV-1 strains in primary macrophages

CCR5 and CXCR4 are the main coreceptors for non-syncytia-inducing (NSI) and syncytia-inducing (SI) HIV-1 strains, respectively. NSI HIV-1 isolates do not infect either human lymphoid or monocytoid cell lines, and this inabili ty correlates with the absence of CCRS expression in these cell types. The ability of SI HIV-1 isolates to infect human primary macrophages has been d isputed. Here, we report that CXCR4 is expressed in primary blood-derived h uman mononuclear phagocytes at all stages of differentiation, although the maturation process correlates with downregulation of CXCR4 mRNA. Infection experiments with the SI molecular clone NL4-3 tagged with a mutant of the g reen fluorescent protein established that both monocytes and attached macro phages are susceptible to infection with CXCR4-restricted HIV-I strains. NL 4-3 entry Into primary macrophages could be blocked by SDF-1 alpha in a dos e-dependent manner, or by the anti-CXCR4 monoclonal antibody 12G5. HIV-1 en try led to productive infection. No evidence of postentry defects or nuclea r import delay for CXCR4 restricted HIV-I strains was detected using a quan titative real-time PCR assay measuring HIV-1 DNA entry into the nucleus. Ma crophages infected by HIV-1 and expressing virus were maintained in culture for long periods of time (up to 5 months). These results demonstrate that GXGR4 is the main HIV-1 SI coreceptor in human primary macrophages and unde rline the importance of the macrophage as a long-living viral reservoir for HIV-1. (C) 2000 Academic Press.