Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells

BACKGROUND: The human placenta-derived cell line BeWo has been demonstrated to be restrictive to cell-free HIV-1 infection. BeWo cells are however permissive to infection by VSV-G pseudotyped HIV-1, which enters cells by a receptor-independent mechanism, and to infection by HIV-1 via a cell-to-cell...

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Autores principales: Ross, Anna Laura, Cannou, Claude, Barré-Sinoussi, Françoise, Menu, Elisabeth
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689159/
https://www.ncbi.nlm.nih.gov/pubmed/19445667
http://dx.doi.org/10.1186/1742-4690-6-46
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author Ross, Anna Laura
Cannou, Claude
Barré-Sinoussi, Françoise
Menu, Elisabeth
author_facet Ross, Anna Laura
Cannou, Claude
Barré-Sinoussi, Françoise
Menu, Elisabeth
author_sort Ross, Anna Laura
collection PubMed
description BACKGROUND: The human placenta-derived cell line BeWo has been demonstrated to be restrictive to cell-free HIV-1 infection. BeWo cells are however permissive to infection by VSV-G pseudotyped HIV-1, which enters cells by a receptor-independent mechanism, and to infection by HIV-1 via a cell-to-cell route. RESULTS: Here we analysed viral entry in wild type BeWo (CCR5(+), CXCR4(+)) and BeWo-CD4(+ )(CD4(+), CCR5(+), CXCR4(+)) cells. We report that HIV-1 internalisation is not restricted in either cell line. Levels of internalised p24 antigen between VSV-G HIV-1 pseudotypes and R5 or X4 virions were comparable. We next analysed the fate of internalised virions; X4 and R5 HIV-1 virions were less stable over time in BeWo cells than VSV-G HIV-1 pseudotypes. We then investigated the role of the proteasome in restricting cell-free HIV-1 infection in BeWo cells using proteasome inhibitors. We observed an increase in the levels of VSV-G pseudotyped HIV-1 infection in proteasome-inhibitor treated cells, but the infection by R5-Env or X4-Env pseudotyped virions remains restricted. CONCLUSION: Collectively these results suggest that cell-free HIV-1 infection encounters a surface block leading to a non-productive entry route, which either actively targets incoming virions for non-proteasomal degradation, and impedes their release into the cytoplasm, or causes the inactivation of mechanisms essential for viral replication.
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spelling pubmed-26891592009-06-02 Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells Ross, Anna Laura Cannou, Claude Barré-Sinoussi, Françoise Menu, Elisabeth Retrovirology Research BACKGROUND: The human placenta-derived cell line BeWo has been demonstrated to be restrictive to cell-free HIV-1 infection. BeWo cells are however permissive to infection by VSV-G pseudotyped HIV-1, which enters cells by a receptor-independent mechanism, and to infection by HIV-1 via a cell-to-cell route. RESULTS: Here we analysed viral entry in wild type BeWo (CCR5(+), CXCR4(+)) and BeWo-CD4(+ )(CD4(+), CCR5(+), CXCR4(+)) cells. We report that HIV-1 internalisation is not restricted in either cell line. Levels of internalised p24 antigen between VSV-G HIV-1 pseudotypes and R5 or X4 virions were comparable. We next analysed the fate of internalised virions; X4 and R5 HIV-1 virions were less stable over time in BeWo cells than VSV-G HIV-1 pseudotypes. We then investigated the role of the proteasome in restricting cell-free HIV-1 infection in BeWo cells using proteasome inhibitors. We observed an increase in the levels of VSV-G pseudotyped HIV-1 infection in proteasome-inhibitor treated cells, but the infection by R5-Env or X4-Env pseudotyped virions remains restricted. CONCLUSION: Collectively these results suggest that cell-free HIV-1 infection encounters a surface block leading to a non-productive entry route, which either actively targets incoming virions for non-proteasomal degradation, and impedes their release into the cytoplasm, or causes the inactivation of mechanisms essential for viral replication. BioMed Central 2009-05-15 /pmc/articles/PMC2689159/ /pubmed/19445667 http://dx.doi.org/10.1186/1742-4690-6-46 Text en Copyright © 2009 Ross 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
Ross, Anna Laura
Cannou, Claude
Barré-Sinoussi, Françoise
Menu, Elisabeth
Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells
title Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells
title_full Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells
title_fullStr Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells
title_full_unstemmed Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells
title_short Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells
title_sort proteasome-independent degradation of hiv-1 in naturally non-permissive human placental trophoblast cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689159/
https://www.ncbi.nlm.nih.gov/pubmed/19445667
http://dx.doi.org/10.1186/1742-4690-6-46
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