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

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...

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Autores principales: Yang, Su Jung, Lopez, Lisa A, Exline, Colin M, Haworth, Kevin G, Cannon, Paula M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192746/
https://www.ncbi.nlm.nih.gov/pubmed/21955466
http://dx.doi.org/10.1186/1742-4690-8-78
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author Yang, Su Jung
Lopez, Lisa A
Exline, Colin M
Haworth, Kevin G
Cannon, Paula M
author_facet Yang, Su Jung
Lopez, Lisa A
Exline, Colin M
Haworth, Kevin G
Cannon, Paula M
author_sort Yang, Su Jung
collection PubMed
description 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 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 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.
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spelling pubmed-31927462011-10-14 Lack of adaptation to human tetherin in HIV-1 Group O and P Yang, Su Jung Lopez, Lisa A Exline, Colin M Haworth, Kevin G Cannon, Paula M Retrovirology Research 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 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 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. BioMed Central 2011-09-28 /pmc/articles/PMC3192746/ /pubmed/21955466 http://dx.doi.org/10.1186/1742-4690-8-78 Text en Copyright ©2011 Yang et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Yang, Su Jung
Lopez, Lisa A
Exline, Colin M
Haworth, Kevin G
Cannon, Paula M
Lack of adaptation to human tetherin in HIV-1 Group O and P
title Lack of adaptation to human tetherin in HIV-1 Group O and P
title_full Lack of adaptation to human tetherin in HIV-1 Group O and P
title_fullStr Lack of adaptation to human tetherin in HIV-1 Group O and P
title_full_unstemmed Lack of adaptation to human tetherin in HIV-1 Group O and P
title_short Lack of adaptation to human tetherin in HIV-1 Group O and P
title_sort lack of adaptation to human tetherin in hiv-1 group o and p
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192746/
https://www.ncbi.nlm.nih.gov/pubmed/21955466
http://dx.doi.org/10.1186/1742-4690-8-78
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