Lack of adaptation to human tetherin in HIV-1 Group O and P

Lack of adaptation to human tetherin in HIV-1 Group O and P

Blog Article

Abstract Background HIV-1 viruses are categorized into four distinct groups: M, N, O and P.Despite the same genomic organization, only the group M viruses are responsible for the world-wide pandemic of AIDS, suggesting better adaptation to human hosts.Previously, it has been reported that the group M Vpu protein is capable of both down-modulating CD4 and counteracting BST-2/tetherin restriction, while the group O Vpu cannot antagonize tetherin.

This led us to investigate if group O, and the related group P viruses, possess functional anti-tetherin activities in Vpu or another viral protein, and to further map the residues required for group M Vpu to counteract human tetherin.Results We found a lack of activity against human tetherin for both the Vpu and Nef proteins from group O and P viruses.Furthermore, we found no evidence of anti-human tetherin activity in a Frying Pan Set fully infectious group O proviral clone, ruling out the possibility of an alternative anti-tetherin factor in this virus.

Interestingly, an activity against primate tetherins was retained Toilet Tissue in the Nef proteins from both a group O and a group P virus.By making chimeras between a functional group M and non-functional group O Vpu protein, we were able to map the first 18 amino acids of group M Vpu as playing an essential role in the ability of the protein to antagonize human tetherin.We further demonstrated the importance of residue alanine-18 for the group M Vpu activity.

This residue lies on a diagonal face of conserved alanines in the TM domain of the protein, and is necessary for specific Vpu-tetherin interactions.Conclusions The absence of human specific anti-tetherin activities in HIV-1 group O and P suggests a failure of these viruses to adapt to human hosts, which may have limited their spread.