Selective transmission of RS-tropic HIV type 1 from dendritic cells to resting CD4(+) T cells

In an in vitro coculture model of monocyte-derived, cultured human dendriti c cells (DC) with autologous CD4(+) resting T cells, CCR5 (RS)-tropic strai ns of HIV-1, but not CXCR4 (X4)-tropic strains, were transmitted to resting CD4(+) T cells, leading to prolific viral output, although DC were suscept ible to infection with either strain. Macrophages, which were also infectab le with either R5- or X4-tropic strains, did not transmit infection to CD4( +) cells. Highly productive HIV infection in this model appeared to be a co nsequence of heterokaryotic syncytium formation between infected DC and T c ells since syncytia formation developed only in R5-infected DC/CD4(+) cocul tures. These results suggested that the unique microenvironment derived fro m the fusion between the infected DC and CD4(+) cell was highly permissive and selective for replication of R5-tropic viruses. The apparent selectivit y for R5-tropic strains in such syncytia was attributable neither to differ ential DC-mediated activation nor to selective modulation of induction of a lpha- or beta -chemokines in the infected DC. This model of HIV replication may provide useful insights into in vitro correlates of HIV pathogenicity.