RT Journal Article SR Electronic(1) A1 Petit, Sarah J. A1 Blondeau, Caroline A1 Towers, Greg J.YR 2011 T1 Analysis of the human immunodeficiency virus type 1 M group Vpu domains involved in antagonizing tetherin JF Journal of General Virology, VO 92 IS 12 SP 2937 OP 2948 DO https://doi.org/10.1099/vir.0.035931-0 PB Microbiology Society, SN 1465-2099, AB Zoonosis of chimpanzee simian immunodeficiency virus cpz to humans has given rise to both pandemic (M) and non-pandemic (O, N and P) groups of human immunodeficiency virus type-1 (HIV). These lentiviruses encode accessory proteins, including Vpu, which has been shown to reduce CD4 levels on the cell surface, as well as increase virion release from the cell by antagonizing tetherin (CD317, BST2). Here, we confirm that O group Vpus (Ca9 and BCF06) are unable to counteract tetherin or downregulate the protein from the cell surface, although they are still able to reduce cell-surface CD4 levels. We hypothesize that this inability to antagonize tetherin may have contributed to O group viruses failing to achieve pandemic levels of human-to-human transmission. Characterization of chimeric O/M group Vpus and Vpu mutants demonstrate that the Vpu–tetherin interaction is complex, involving several domains. We identify specific residues within the transmembrane proximal region that, along with the transmembrane domain, are crucial for tetherin counteraction and enhanced virion release. We have also shown that the critical domains are responsible for the localization of M group Vpu to the trans-Golgi network, where it relocalizes tetherin to counteract its function. This work sheds light on the acquisition of anti-tetherin activity and the molecular details of pandemic HIV infection in humans., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.035931-0