the hiv-1 vpu viroporin inhibitor bit225 does not affect vpu-mediated tetherin antagonism的hiv - 1 vpu viroporin抑制剂bit225并不影响vpu-mediated tetherin对抗.pdf

The HIV-1 Vpu Viroporin Inhibitor BIT225 Does Not Affect Vpu-Mediated Tetherin Antagonism ¨ 1,2¤ 1,2 1,3 1 1,2,3 Bjorn D. Kuhl , Vicky Cheng , Daniel A. Donahue , Richard D. Sloan , Chen Liang , John Wilkinson4, Mark A. Wainberg1,2,3* ´ 1 McGill University AIDS Center, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada, 2 Department of Experimental Medicine, McGill University, ´ ´ Montreal, Canada, 3 Department of Microbiology and Immunology, McGill University, Montreal, Canada, 4 Biotron Limited, St Vincent’s Centre for Applied Medical Research, Sydney, Australia Abstract Among its many roles, the HIV-1 accessory protein Vpu performs a viroporin function and also antagonizes the host cell restriction factor tetherin through its transmembrane domain. BIT225 is a small molecule inhibitor that specifically targets the Vpu viroporin function, which, in macrophages, resulted in late stage inhibition of virus release and decreased infectivity of released virus, a phenotype similar to tetherin-mediated restriction. Here, we investigated whether BIT225 might mediate its antiviral function, at least in part, via inhibition of Vpu-mediated tetherin antagonism. Using T-cell lines inducible for tetherin expression, we found that BIT225 does not exert its antiviral function by inhibiting Vpu-mediated tetherin downmodulation from the cell surface, the main sit