The transmembrane domain of HIV-1 Vpu is sufficient to confer anti-tetherin activity to SIVcpz and SIVgor Vpus [thesis]

Silvia Franziska Kluge, Universität Ulm
The acquisition of effective Vpu-mediated anti-tetherin activity distinguishes pandemic HIV-1 group M strains from non-pandemic group N, O and P viruses and may have been a prerequisite for their global spread. Sequence analyses revealed that the motifs in the cytoplasmic tail of Vpu reported to be required for effective antagonism of human tetherin are often conserved in SIVcpzPtt Vpus from Central chimpanzees but usually absent in SIVcpzPts Vpus from Eastern chimpanzees and SIVgor Vpus from
more » ... stern lowland gorillas. The aim of my thesis was to clarify whether the SIVcpzPtt Vpu only requires adaptive changes in the transmembrane domain whereas SIVcpzPts or SIVgor Vpus require adaptation in both TMD and cytoplasmic part to acquire activity against the human tetherin orthologue. This might explain (1) why SIVcpzPts has never been detected in humans yet and (2) why the descendants of SIVcpzPtt but not SIVgor evolved Vpu-mediated tetherin antagonism and caused the AIDS pandemic. My results suggest that it is easier for SIVcpzPts and SIVgor to evolve Vpu-mediated anti-human tetherin activity than previously anticipated. The data further demonstrate that the requirements for trafficking and beta-TrCP binding motifs in the cytoplasmic part of Vpu for human tetherin counteraction are highly context dependent. Thus, results obtained from the analysis a few T cell line adapted HIV-1 strains should not be generalized.
doi:10.18725/oparu-3436 fatcat:euu6gntmc5fyzgdyugiq7n4ika