HIV-1 Entry in SupT1-R5, CEM-ss, and Primary CD4⁺T Cells Occurs at the Plasma Membrane and Does Not Require Endocytosis

Distinct Requirements for HIV-Cell Fusion and HIV-mediated Cell-Cell Fusion

“…Our finding that actin inhibitors also reduce the efficiency of virus uptake by CEM.CCR5 cells is consistent with published data on the actin dependence of HIV-1 uptake by CD4 ϩ T cells (83). Although these results do not rule out the possibility of HIV-1 fusion with the PM of lymphoid cells, as reported previously (24), the proportional decrease in the virus uptake and fusion in CEM.CCR5 cells pretreated with actin inhibitors is in line with fusion occurring after CD4/coreceptor-mediated and actin-dependent endocytosis. This notion is further supported by the requirement for intact actin for acid-mediated VSVpp fusion with CEM.CCR5 cells.…”

“…The actin dependence of HIV-1 fusion with CEM.CCR5 cells could be indicative of virus fusion with the plasma membrane, as has been recently suggested (24). However, the diminished VSVpp fusion with acidic endosomes (64) in the presence of actin inhibitors suggests that actin may be involved in productive virus uptake by these cells rather than the fusion step itself.…”

“…5C). The incomplete inhibition of virus-cell fusion by C52L added at this stage is likely due to a low level HIV-cell fusion and/or productive endocytosis occurring upon prolonged incubation at 20°C (12,24).…”

“…Attempts to redirect HIV-1 fusion to the cell surface by blocking its uptake were unsuccessful (12). However, a recent study of HIV-1 fusion with lymphoid cells has concluded that endocytosis does not contribute to productive entry (24). Moreover, the ability of HIV-1 Env expressed on the cell surface to promote fusion with target cells (25)(26)(27) as well as the ability of HIV-1 particles to mediate fusion between adjacent cells (a phenomenon commonly referred to as "fusion-fromwithout", FFWO) (28) demonstrate that this virus can fuse with the PM.…”

Resolving the Sites of HIV Entry: Dynamin Networks Hold the Key

“…Like certain enveloped viruses such as Herpes Simplex virus-1 and Sendai virus, HIV entry was shown to be independent of pH and/or presence of lysosomal enzymes thus suggesting that virus entry into endolysosomal compartments was not required [19][20][21][22][23][24][25][26][27][28][29][30][31]. Studies with CD4 truncation mutations supported this view as mutations that tethered CD4 at the membrane did not impede HIV entry [20,22,23].…”