HIV ENTRY INTO CELLS BY CD4-INDEPENDENT MECHANISMS

All HIV and SIV strains can enter cells by binding to cell-surface CD4 . Therapeutics designed to intervene in viral entry by blocking HIV at tachment to CD4, may not work if entry mechanisms independent of CD4 o ccur frequently in vivo. A. range of cell-surface molecules as well as CD4 can bind gp120, yet few act as receptors for HIV infection, indic ating that passive attachment to the cell surface is not sufficient to confer virus entry, In vitro, HIV entry independent of CD4 has freque ntly been described, although this route to infection is usually ineff icient. Variants of HIV-1 and HIV-2 that infect CD4-negative cell type s more efficiently can be selected in vitro. However, there is current ly no evidence that such variants evolve in vivo. Furthermore, present knowledge suggests that few CD4-negative cells types are productively infected in vivo. It is thus unlikely that CD4-independent infection significantly influences HIV induced pathogenesis in vivo.