CELL-SURFACE DOWN-MODULATION OF CD4 AFTER INFECTION

Entry of HIV-1 into host cells is generally mediated by the cell surfa ce CD4 receptor after specific interaction with the viral envelope gly coprotein gp120. Infection by HIV-1 commonly leads to the disappearanc e of CD4 from the plasma membrane, a phenomenon referred to as recepto r down-modulation, This, in turn, renders cells refractory to subseque nt infection by the same or other viruses that use the CD4 receptor fo r entry, creating a state of superinfection immunity. CD4 down-modulat ion is a complex process involving a variety of viral gene products, t he effects of which may be manifest at different stages within the vir al replication cycle. CD4 disappearance from the cell surface occurs i n each of the CD4 + lymphocytes, T-cell lines, monocytic cell lines, a nd monocyte-derived macrophages. Internalization of CD4 can occur afte r binding of either gp120 alone of gp120 antigen-antibody complexes, a nd may also be mediated by the HIV-1 Nef gene. Other factors that caus e cell surface CD4 depletion include reductions in CD4 transcript leve ls, impaired translation of CD4 mRNA, formation of CD4-gp160 intracell ular complexes, and degradation of CD4 mediated by the HIV-1 Vpu gene.