Is Necessary, But Not Sufficient, for HIV-1 Entry

while CD4 is necessary for HIV-1 entry into susceptible cells, not all cells expressing CD4 became infected by the virus (as reviewed in 20). Mouse cells expressing human CD4 are deficient for viral entry (21). Interestingly, when certain human chromosomes were added to these cells, the block to viral entry was overcome, indicating that a second factor was necessary at this early step (22). The second receptor appeared to be necessary for viral fusion (22). 

In addition to the above, laboratory strains of HIV-1 exhibited a cellular tropism distinct from that of many primary HIV-1 isolates. All isolates of HIV-1 are able to infect primary T lymphocytes. However, as viral stocks were cultured and expanded in the laboratory, they gained a greater ability to infect T cell lines and lost the ability to infect macrophages. At least three distinct phenotypes were observed primary isolates that infected primary T cells and macrophages (M-tropic), primary isolates that infected primary T cells and macrophages as well as T cell lines (dual-tropic), and laboratory-adapted isolates able to infect primary T cells and T cell lines (T-tropic). Cellular tropism was then found to be conferred by the V3 loop of gpl20 (23,24). 

In view of the above, several groups searched for the coreceptor(s) needed by CD4 for HIV entry into cells. The results of these studies clarified why chemokines can inhibit HIV replication. It was shown that the principal coreceptor for 

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Indicated are the 13 seven-transmembrane-domain G-protein-coupled-receptors (7TM-GPCR) identified as functional coreceptors for HIV infection when recombinant protein is expressed on transfected cells in vitro. The known ligands, expression pattern on peripheral blood lymphocytes (PEL) and monocyte/macrophages, and ability to function as an HIV coreceptor on primary cells are indicated. CCR5 and CXCR4 are the most significant coreceptors in vivo. 

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