Variable infectivity and conserved engagement in cell-to-cell viral transfer by HIV-1 Env from Clade B transmitted founder clones

HIV-1 transmission is usually initiated by a single viral strain called transmitted/ founder (T/F) virus. In in vitro models, HIV-1 can efficiently spread via cell-free and virological synapse (VS)-mediated cell-to-cell infection. Both modes of infection require the viral glycoprotein Envelope (Env). The efficiency with which T/F Envs initiate VS and mediate cell-to-cell infection has not been well characterized. Here we tested a panel of isogenic HIV-1 molecular clones that carry different Clade B T/F Envs. We found that despite variable infectivity among different Env clones in the two modes of infection, T/F Envs generally mediated efficient VS formation and subsequent cell-to-cell transfer. In contrast, in vitro infectivity of the T/F Env clones was more variable and strongly correlated with intrinsic fusogenicity of various Envs. We speculate that the conservation of cell-to-cell transfer by T/F Env is indicative of a biologically important function of Env.