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Inhibition of HIV-1 assembly by coiled-coil domain containing protein 8 in human cells.
Sci Rep. 2015 Oct 01; 5:14724.SR

Abstract

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.

Authors+Show Affiliations

School of Medicine, Nankai University, Tianjin, China, 300071. Lady Davis Institute, Jewish General Hospital, McGill University, Canada, H3T 1E2. State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.Lady Davis Institute, Jewish General Hospital, McGill University, Canada, H3T 1E2.State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.Lady Davis Institute, Jewish General Hospital, McGill University, Canada, H3T 1E2.Lady Davis Institute, Jewish General Hospital, McGill University, Canada, H3T 1E2.Lady Davis Institute, Jewish General Hospital, McGill University, Canada, H3T 1E2.School of Medicine, Nankai University, Tianjin, China, 300071. State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. Peking University Health Science Center, Beijing, China.Lady Davis Institute, Jewish General Hospital, McGill University, Canada, H3T 1E2.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26423533

Citation

Wei, Min, et al. "Inhibition of HIV-1 Assembly By Coiled-coil Domain Containing Protein 8 in Human Cells." Scientific Reports, vol. 5, 2015, p. 14724.
Wei M, Zhao X, Liu M, et al. Inhibition of HIV-1 assembly by coiled-coil domain containing protein 8 in human cells. Sci Rep. 2015;5:14724.
Wei, M., Zhao, X., Liu, M., Huang, Z., Xiao, Y., Niu, M., Shao, Y., & Kleiman, L. (2015). Inhibition of HIV-1 assembly by coiled-coil domain containing protein 8 in human cells. Scientific Reports, 5, 14724. https://doi.org/10.1038/srep14724
Wei M, et al. Inhibition of HIV-1 Assembly By Coiled-coil Domain Containing Protein 8 in Human Cells. Sci Rep. 2015 Oct 1;5:14724. PubMed PMID: 26423533.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of HIV-1 assembly by coiled-coil domain containing protein 8 in human cells. AU - Wei,Min, AU - Zhao,Xia, AU - Liu,Mi, AU - Huang,Zhi, AU - Xiao,Yong, AU - Niu,Meijuan, AU - Shao,Yiming, AU - Kleiman,Lawrence, Y1 - 2015/10/01/ PY - 2015/02/02/received PY - 2015/09/03/accepted PY - 2015/10/2/entrez PY - 2015/10/2/pubmed PY - 2016/8/20/medline SP - 14724 EP - 14724 JF - Scientific reports JO - Sci Rep VL - 5 N2 - 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. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/26423533/Inhibition_of_HIV_1_assembly_by_coiled_coil_domain_containing_protein_8_in_human_cells_ L2 - http://dx.doi.org/10.1038/srep14724 DB - PRIME DP - Unbound Medicine ER -