CD4 and HIV-1 infection: Several lines of evidence have been reported for the plasma membrane being the primary site of HIV-1 entry: (i) the endocytic signal peptide in CD4 is dispensable for HIV-1 infection [7]; (ii) expression of HIV-Env efficiently mediates cell-to-cell fusion [8]; and (iii) HIV-1 infection is not dependent on a low-pH cue [4,9].