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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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2009
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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. |
format | Text |
id | pubmed-2689159 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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