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Inhibition of HIV-1 assembly by coiled-coil domain containing protein 8 in human cells
Human Immunodeficiency Virus type 1 (HIV-1) major structure protein Gag is synthesized in the cytoplasm, assembles on the plasma membrane, subsequently buds and releases. HIV-1 viral particles incorporate a number of host proteins to facilitate or inhibit HIV-1 replication. Here we identify a new ho...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589731/ https://www.ncbi.nlm.nih.gov/pubmed/26423533 http://dx.doi.org/10.1038/srep14724 |
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author | Wei, Min Zhao, Xia Liu, Mi Huang, Zhi Xiao, Yong Niu, Meijuan Shao, Yiming Kleiman, Lawrence |
author_facet | Wei, Min Zhao, Xia Liu, Mi Huang, Zhi Xiao, Yong Niu, Meijuan Shao, Yiming Kleiman, Lawrence |
author_sort | Wei, Min |
collection | PubMed |
description | Human Immunodeficiency Virus type 1 (HIV-1) major structure protein Gag is synthesized in the cytoplasm, assembles on the plasma membrane, subsequently buds and releases. HIV-1 viral particles incorporate a number of host proteins to facilitate or inhibit HIV-1 replication. Here we identify a new host protein, coiled-coil domain containing protein 8 (CCDC8), in HIV-1 particles. Incorporation of CCDC8 into virions is dependent on the interaction between CCDC8 and Gag matrix region. Exogenous overexpression of CCDC8 can strongly inhibit HIV-1 production, up to ~30 fold. CCDC8 is a membrane-associated protein. The interaction between exogenously expressed CCDC8 and Gag on the plasma membrane changes the assembly of Gag, and redirects it into intracellular sites, or causes Gag endocytosis. CCDC8, along with cytoskeleton protein obscuring-like1 (Obsl1) and E3 ligase Cul7, induces Gag polyubiquitination and degradation. Thus we identify a new host protein and a new pathway for HIV-1 Gag polyubiquitination and degradation. This pathway presents potential therapeutic strategies against HIV infection. |
format | Online Article Text |
id | pubmed-4589731 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45897312015-10-13 Inhibition of HIV-1 assembly by coiled-coil domain containing protein 8 in human cells Wei, Min Zhao, Xia Liu, Mi Huang, Zhi Xiao, Yong Niu, Meijuan Shao, Yiming Kleiman, Lawrence Sci Rep Article Human Immunodeficiency Virus type 1 (HIV-1) major structure protein Gag is synthesized in the cytoplasm, assembles on the plasma membrane, subsequently buds and releases. HIV-1 viral particles incorporate a number of host proteins to facilitate or inhibit HIV-1 replication. Here we identify a new host protein, coiled-coil domain containing protein 8 (CCDC8), in HIV-1 particles. Incorporation of CCDC8 into virions is dependent on the interaction between CCDC8 and Gag matrix region. Exogenous overexpression of CCDC8 can strongly inhibit HIV-1 production, up to ~30 fold. CCDC8 is a membrane-associated protein. The interaction between exogenously expressed CCDC8 and Gag on the plasma membrane changes the assembly of Gag, and redirects it into intracellular sites, or causes Gag endocytosis. CCDC8, along with cytoskeleton protein obscuring-like1 (Obsl1) and E3 ligase Cul7, induces Gag polyubiquitination and degradation. Thus we identify a new host protein and a new pathway for HIV-1 Gag polyubiquitination and degradation. This pathway presents potential therapeutic strategies against HIV infection. Nature Publishing Group 2015-10-01 /pmc/articles/PMC4589731/ /pubmed/26423533 http://dx.doi.org/10.1038/srep14724 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Wei, Min Zhao, Xia Liu, Mi Huang, Zhi Xiao, Yong Niu, Meijuan Shao, Yiming Kleiman, Lawrence Inhibition of HIV-1 assembly by coiled-coil domain containing protein 8 in human cells |
title | Inhibition of HIV-1 assembly by coiled-coil domain containing protein 8 in human cells |
title_full | Inhibition of HIV-1 assembly by coiled-coil domain containing protein 8 in human cells |
title_fullStr | Inhibition of HIV-1 assembly by coiled-coil domain containing protein 8 in human cells |
title_full_unstemmed | Inhibition of HIV-1 assembly by coiled-coil domain containing protein 8 in human cells |
title_short | Inhibition of HIV-1 assembly by coiled-coil domain containing protein 8 in human cells |
title_sort | inhibition of hiv-1 assembly by coiled-coil domain containing protein 8 in human cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589731/ https://www.ncbi.nlm.nih.gov/pubmed/26423533 http://dx.doi.org/10.1038/srep14724 |
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