Anti-tetherin activities in Vpu-expressing primate lentiviruses.
Retrovirology
; 7: 13, 2010 Feb 18.
Article
in En
| MEDLINE
| ID: mdl-20167081
ABSTRACT
BACKGROUND:
The anti-viral activity of the cellular restriction factor, BST-2/tetherin, was first observed as an ability to block the release of Vpu-minus HIV-1 from the surface of infected cells. However, tetherin restriction is also counteracted by primate lentiviruses that do not express a Vpu protein, where anti-tetherin functions are provided by either the Env protein (HIV-2, SIVtan) or the Nef protein (SIVsm/mac and SIVagm). Within the primate lentiviruses, Vpu is also present in the genomes of SIVcpz and certain SIVsyk viruses. We asked whether, in these viruses, anti-tetherin activity was always a property of Vpu, or if it had selectively evolved in HIV-1 to perform this function.RESULTS:
We found that despite the close relatedness of HIV-1 and SIVcpz, the chimpanzee viruses use Nef instead of Vpu to counteract tetherin. Furthermore, SIVcpz Nef proteins had activity against chimpanzee but not human tetherin. This specificity mapped to a short sequence that is present in the cytoplasmic tail of primate but not human tetherins, and this also accounts for the specificity of SIVsm/mac Nef for primate but not human tetherins. In contrast, Vpu proteins from four diverse members of the SIVsyk lineage all displayed an anti-tetherin activity that was active against macaque tetherin. Interestingly, Vpu from a SIVgsn isolate was also found to have activity against human tetherin.CONCLUSIONS:
Primate lentiviruses show a high degree of flexibility in their use of anti-tetherin factors, indicating a strong selective pressure to counteract tetherin restriction. The identification of an activity against human tetherin in SIVgsn Vpu suggests that the presence of Vpu in the ancestral SIVmus/mon/gsn virus believed to have contributed the 3' half of the HIV-1 genome may have played a role in the evolution of viruses that could counteract human tetherin and infect humans.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Virus Replication
/
Antigens, CD
/
Lentiviruses, Primate
/
Human Immunodeficiency Virus Proteins
/
Viral Regulatory and Accessory Proteins
/
Virus Release
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Retrovirology
Journal subject:
VIROLOGIA
Year:
2010
Document type:
Article
Affiliation country:
Estados Unidos