The HIV-2 genotype and the HIV-1 syncytium-inducing phenotype are associated with a lower virus replication in dendritic cells

During sexual transmission, HIV infects the mucosal dendritic cells and is transferred to CD4 T cells. Whether HIV variants of a particular genetic (s ub)type or phenotype selectively infect dendritic cells (DC) or are prefere ntially transferred to T cells remains highly controversial. To avoid the c umbersome use of primary dendritic cells, in vitro dendritic cell models we re generated from precursors, either hematopoietic progenitor cells (HPC) o r monocytes (MO). Productive infection in the dendritic cells and transfer of the virus to T cells was assessed for a range of HIV variants. HPC-deriv ed dendritic cells (HPC-DC) were more susceptible to HIV-1 than to HIV-2 is olates. The HIV-1 group O strains were more productive in HPC-DC than group M, but amongst the latter, no subtype-related difference was observed. Bot h non-syncytium-inducing (NSI) and SI HIV isolates and lab strains could pr oductively infect HPC-DC, albeit with a different efficiency. Adding blocki ng antibodies confirmed that both CCR-5 and CXCR-4 coreceptors were functio nal. Biological HIV-1 clones of the NSI/R5 phenotype infected more readily HPC-DC than SI/X4 clones. MO-derived dendritic cells were, however, more ex clusive in their preference for NSI/R5 clones. Some HIV variants, that did not grow readily in HPC-DC alone, could be rescued by adding resting or pre -activated T cells. The present data show that HIV-2 isolates and SI clones replicate less in model-DC, but no preference for a particular HIV-1 subty pe was evident. Co-culture with T cells could "correct" a limited growth in dendritic cells. Clearly, both intrinsic dendritic cell susceptibility and enhancement by T cells are explained only partly by HIV genotype and pheno type. The in vitro dendritic cell models seem useful tools to further unrav el interactions between HIV, DC, and T cells. J, Med. Virol. 60:300-312, 20 00. (C) 2000 Wiley-Liss, Inc.