
<ArticleTitle>Molecular basis for cell tropism of <prot>CXCR4</prot>-dependent human immunodeficiency virus type 1 isolates.</ArticleTitle>
<AbstractText>Laboratory isolates of human immunodeficiency virus type 1 (HIV-1) that utilize <prot>CXCR4</prot> as a coreceptor infect primary human macrophages inefficiently even though these express a low but detectable level of cell surface <prot>CXCR4</prot>. In contrast, infection of primary macrophages by primary <prot>CXCR4</prot>-tropic HIV-1 isolates is readily detectable. Here, we provide evidence suggesting that this difference in cell tropism results from a higher requirement for cell surface <prot>CXCR4</prot> for infection by laboratory HIV-1 isolates. Transfected COS7 cells that express a high level of <prot>CD4</prot> but a low level of <prot>CXCR4</prot> were infected significantly more efficiently by two primary <prot>CXCR4</prot>-tropic HIV-1 isolates compared to the prototypic laboratory HIV-1 isolate IIIB. More importantly, overexpression of either wild-type or signaling-defective <prot>CXCR4</prot> on primary macrophages dramatically enhanced the efficiency of infection by the laboratory HIV-1 isolate yet only modestly enhanced infection by either primary <prot>CXCR4</prot>-tropic virus. Overexpression of <prot>CD4</prot> had, in contrast, only a limited effect on macrophage infection by the laboratory HIV-1, although infection by the primary isolates was markedly enhanced. We therefore conclude that the laboratory <prot>CXCR4</prot>-tropic HIV-1 isolate exhibits a significantly higher <prot>CXCR4</prot> requirement for efficient infection than do the primary <prot>CXCR4</prot>-tropic isolates and that this difference can explain the poor ability of the laboratory HIV-1 isolate to replicate in primary macrophages. More generally, we propose that the cell tropisms displayed by different strains of HIV-1 in culture can largely be explained on the basis of differential requirements for cell surface <prot>CD4</prot> and/or coreceptor expression levels.</AbstractText>
