Cell-cell transmission allows human T-lymphotropic virus 1 to circumvent tetherin restriction.

Tetherin is part of the cellular innate immunity and impedes cell-free transmission of viruses that bud from the plasma membrane by retaining them on the cell surface. Some viruses have evolved activities in different proteins such as Vpu (HIV-1), K-protein (KSHV), Nef (SIV) or Env (HIV-2) to downregulate tetherin and overcome its restriction. We found that chronically HTLV-1 infected T-cell lines express eightfold more tetherin than uninfected transformed T-cell lines suggesting that tetherin expression is not inhibited by the virus. We observed that even small amounts of exogenous tetherin caused the retention of HTLV-1 on the cell surface and severely reduced cell-free infectivity of HTLV-1, but that cell-cell transmission, which is more relevant for HTLV-1, was significantly less decreased. However, knock-down of tetherin expresssion resulted in a slight increase in cell-cell infection indicating that the protein does not enhance this route of transmission.