Figure 6

Adaptations of primate lentiviruses during cross-species transmission and the emergence of pandemic HIV-1 strains. The SIV from chimpanzee is believed to result from recombination events through successive cross-species transmission between the precursors of the SIVgsn/mon/mus and the SIVrcm lineages. The transmembrane domain of Tetherin evolved primarily during transition from the non hominoïd lineage to the hominoïd lineage, explaining why the Vpu protein inherited from the SIVgsn/mon/mus lineage does not exhibit any activity against chimpanzee Tetherin. After transmission from chimpanzees to humans, SIVcpz was unable anymore to use Nef to counteract Tetherin due to a deletion of five amino acids in the cytoplasmic domain of human Tetherin, which usually confers responsiveness to Nef. During evolution/adaptation from SIVcpz to HIV-1, modifications mapped to two regions of the Vpu transmembrane domain have conferred human Tetherin a susceptibility to Vpu, except in the case of the HIV-1 group O. Furthermore, the HIV-1 group N Vpu somehow has lost its ability to mediate CD4 degradation in the process. Only the pandemic HIV-1 group M harbors the two primary Vpu functions. Susceptibility of the transmembrane domain of Tetherin to Vpu is represented by similar colour pairing. The deletion of the five amino acids in human Tetherin cytoplamic tail is represented by the absence of the D/GDIWK sequence. The color gradient indicates co-evolution between SIV/HIV and host.