Mechanism of HIV-1 entry into CD4+ T cells

Although the mechanism responsible for HIV-1 entry into susceptible CD4+ T cells is incompletely understood, a number of key components are now known. For example, the tropism of HIV-1 for cells expressing the CD4 membrane glycoprotein reflects the use of this protein as a specific viral receptor to which the HIV-1 gp120 envelope protein binds with high affinity. This binding apparently results in the exposure of hydrophobic domains of the gp41 transmembrane protein to apposing plasma membrane components, resulting in the fusion of viral and plasma membranes to one another which, in turn, releases HIV-1 RNA into the cytosol. This fusion event, which is requisite for viral entry as well as HIV-1 associated syncytia formation, occurs in a pH-independent fashion, but requires antecedent T cell activation. In the absence of T cell stimuli, resting CD4+ cells are resistant to HIV-1 entry, which may explain the observation that at any given time the vast majority of CD4+ T cells in HIV-1 seropositive patients are not infected despite the presence of relatively large quantities of free virus in the blood of such patients. The mechanism of HIV-1 entry into other CD4+ cell types, such as macrophages and dendritic cells, remains to be determined.