title: DDX5 facilitates HIV-1 replication as a cellular co-factor of Rev.
abstract: HIV-1 Rev plays an important role in the late phase of HIV-1 replication, which facilitates export of unspliced viral mRNAs from the nucleus to cytoplasm in infected cells. Recent studies have shown that DDX1 and DDX3 are co-factors of Rev for the export of HIV-1 transcripts. In this report, we have demonstrated that DDX5 (p68), which is a multifunctional DEAD-box RNA helicase, functions as a new cellular co-factor of HIV-1 Rev. We found that DDX5 affects Rev function through the Rev-RRE axis and subsequently enhances HIV-1 replication. Confocal microscopy and co-immunoprecipitation analysis indicated that DDX5 binds to Rev and this interaction is largely dependent on RNA. If the DEAD-box motif of DDX5 is mutated, DDX5 loses almost all of its ability to bind to Rev, indicating that the DEAD-box motif of DDX5 is required for the interaction between DDX5 and Rev. Our data indicate that interference of DDX5-Rev interaction could reduce HIV-1 replication and potentially provide a new molecular target for anti-HIV-1 therapeutics.
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiuxia
authors.initials: X
authors.lastname: Zhou
authors.forename: Juan
authors.initials: J
authors.lastname: Luo
authors.forename: Lisa
authors.initials: L
authors.lastname: Mills
authors.forename: Shuangxin
authors.initials: S
authors.lastname: Wu
authors.forename: Ting
authors.initials: T
authors.lastname: Pan
authors.forename: Guannan
authors.initials: G
authors.lastname: Geng
authors.forename: Jim
authors.initials: J
authors.lastname: Zhang
authors.forename: Haihua
authors.initials: H
authors.lastname: Luo
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
mesh_terms: D021581:Active Transport, Cell Nucleus; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D017930:Genes, Reporter; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020218:Response Elements; D014779:Virus Replication; D054321:rev Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D054321:rev Gene Products, Human Immunodeficiency Virus; C506749:Ddx5 protein, human; D053487:DEAD-box RNA Helicases