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High level of susceptibility to human TRIM5α conferred by HIV-2 capsid sequences

BACKGROUND: HIV-2, which was transmitted to humans from a distant primate species (sooty mangabey), differs remarkably from HIV-1 in its infectivity, transmissibility and pathogenicity. We have tested the possibility that a greater susceptibility of HIV-2 capsid (CA) to the human restriction factor...

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Autores principales: Takeuchi, Junko S, Perche, Benjamin, Migraine, Julie, Mercier-Delarue, Séverine, Ponscarme, Diane, Simon, François, Clavel, François, Labrosse, Béatrice
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691696/
https://www.ncbi.nlm.nih.gov/pubmed/23647667
http://dx.doi.org/10.1186/1742-4690-10-50
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author Takeuchi, Junko S
Perche, Benjamin
Migraine, Julie
Mercier-Delarue, Séverine
Ponscarme, Diane
Simon, François
Clavel, François
Labrosse, Béatrice
author_facet Takeuchi, Junko S
Perche, Benjamin
Migraine, Julie
Mercier-Delarue, Séverine
Ponscarme, Diane
Simon, François
Clavel, François
Labrosse, Béatrice
author_sort Takeuchi, Junko S
collection PubMed
description BACKGROUND: HIV-2, which was transmitted to humans from a distant primate species (sooty mangabey), differs remarkably from HIV-1 in its infectivity, transmissibility and pathogenicity. We have tested the possibility that a greater susceptibility of HIV-2 capsid (CA) to the human restriction factor TRIM5α (hTRIM5α) could contribute to these differences. RESULTS: We constructed recombinant clones expressing CA from a variety of HIV-2 viruses in the context of HIV-1 NL4-3-luciferase. CA sequences were amplified from the plasma of HIV-2 infected patients, including 8 subtype A and 7 subtype B viruses. CA from 6 non-epidemic HIV-2 subtypes, 3 HIV-2 CRF01_AB recombinants and 4 SIVsmm viruses were also tested. Susceptibility to hTRIM5α was measured by comparing single-cycle infectivity in human target cells expressing hTRIM5α to that measured in cells in which hTRIM5α activity was inhibited by overexpression of hTRIM5γ. The insertion of HIV-2 CA sequences in the context of HIV-1 did not affect expression and maturation of the HIV-2 CA protein. The level of susceptibility hTRIM5α expressed by viruses carrying HIV-2 CA sequences was up to 9-fold higher than that of HIV-1 NL4-3 and markedly higher than a panel of primary HIV-1 CA sequences. This phenotype was found both for viruses carrying CA from primary HIV-2 sequences and viruses carrying CA from laboratory-adapted HIV-2 clones. High hTRIM5α susceptibility was found in all HIV-2 subtypes. In this series of viruses, susceptibility to hTRIM5α was not significantly affected by the presence of a proline at position 119 or by the number of prolines at positions 119, 159 or 178 in HIV-2 CA. No significant correlation was found between HIV-2 viremia and sensitivity to hTRIM5α. CONCLUSIONS: HIV-2 capsid sequences expressed high levels of susceptibility to hTRIM5α. This property, common to all HIV-2 sequences tested, may contribute in part to the lower replication and pathogenicity of this virus in humans.
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spelling pubmed-36916962013-06-26 High level of susceptibility to human TRIM5α conferred by HIV-2 capsid sequences Takeuchi, Junko S Perche, Benjamin Migraine, Julie Mercier-Delarue, Séverine Ponscarme, Diane Simon, François Clavel, François Labrosse, Béatrice Retrovirology Research BACKGROUND: HIV-2, which was transmitted to humans from a distant primate species (sooty mangabey), differs remarkably from HIV-1 in its infectivity, transmissibility and pathogenicity. We have tested the possibility that a greater susceptibility of HIV-2 capsid (CA) to the human restriction factor TRIM5α (hTRIM5α) could contribute to these differences. RESULTS: We constructed recombinant clones expressing CA from a variety of HIV-2 viruses in the context of HIV-1 NL4-3-luciferase. CA sequences were amplified from the plasma of HIV-2 infected patients, including 8 subtype A and 7 subtype B viruses. CA from 6 non-epidemic HIV-2 subtypes, 3 HIV-2 CRF01_AB recombinants and 4 SIVsmm viruses were also tested. Susceptibility to hTRIM5α was measured by comparing single-cycle infectivity in human target cells expressing hTRIM5α to that measured in cells in which hTRIM5α activity was inhibited by overexpression of hTRIM5γ. The insertion of HIV-2 CA sequences in the context of HIV-1 did not affect expression and maturation of the HIV-2 CA protein. The level of susceptibility hTRIM5α expressed by viruses carrying HIV-2 CA sequences was up to 9-fold higher than that of HIV-1 NL4-3 and markedly higher than a panel of primary HIV-1 CA sequences. This phenotype was found both for viruses carrying CA from primary HIV-2 sequences and viruses carrying CA from laboratory-adapted HIV-2 clones. High hTRIM5α susceptibility was found in all HIV-2 subtypes. In this series of viruses, susceptibility to hTRIM5α was not significantly affected by the presence of a proline at position 119 or by the number of prolines at positions 119, 159 or 178 in HIV-2 CA. No significant correlation was found between HIV-2 viremia and sensitivity to hTRIM5α. CONCLUSIONS: HIV-2 capsid sequences expressed high levels of susceptibility to hTRIM5α. This property, common to all HIV-2 sequences tested, may contribute in part to the lower replication and pathogenicity of this virus in humans. BioMed Central 2013-05-06 /pmc/articles/PMC3691696/ /pubmed/23647667 http://dx.doi.org/10.1186/1742-4690-10-50 Text en Copyright © 2013 Takeuchi 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
Takeuchi, Junko S
Perche, Benjamin
Migraine, Julie
Mercier-Delarue, Séverine
Ponscarme, Diane
Simon, François
Clavel, François
Labrosse, Béatrice
High level of susceptibility to human TRIM5α conferred by HIV-2 capsid sequences
title High level of susceptibility to human TRIM5α conferred by HIV-2 capsid sequences
title_full High level of susceptibility to human TRIM5α conferred by HIV-2 capsid sequences
title_fullStr High level of susceptibility to human TRIM5α conferred by HIV-2 capsid sequences
title_full_unstemmed High level of susceptibility to human TRIM5α conferred by HIV-2 capsid sequences
title_short High level of susceptibility to human TRIM5α conferred by HIV-2 capsid sequences
title_sort high level of susceptibility to human trim5α conferred by hiv-2 capsid sequences
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691696/
https://www.ncbi.nlm.nih.gov/pubmed/23647667
http://dx.doi.org/10.1186/1742-4690-10-50
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