title: Human DDX3 interacts with the HIV-1 Tat protein to facilitate viral mRNA translation.
abstract: Nuclear export and translation of intron-containing viral mRNAs are required for HIV-1 gene expression and replication. In this report, we provide evidence to show that DDX3 regulates the translation of HIV-1 mRNAs. We found that knockdown of DDX3 expression effectively inhibited HIV-1 production. Translation of HIV-1 early regulatory proteins, Tat and rev, was impaired in DDX3-depleted cells. All HIV-1 transcripts share a highly structured 5' untranslated region (UTR) with inhibitory elements on translation of viral mRNAs, yet DDX3 promoted translation of reporter mRNAs containing the HIV-1 5' UTR, especially with the transactivation response (TAR) hairpin. Interestingly, DDX3 directly interacts with HIV-1 Tat, a well-characterized transcriptional activator bound to the TAR hairpin. HIV-1 Tat is partially targeted to cytoplasmic stress granules upon DDX3 overexpression or cell stress conditions, suggesting a potential role of Tat/DDX3 complex in translation. We further demonstrated that HIV-1 Tat remains associated with translating mRNAs and facilitates translation of mRNAs containing the HIV-1 5' UTR. Taken together, these findings indicate that DDX3 is recruited to the TAR hairpin by interaction with viral Tat to facilitate HIV-1 mRNA translation.
authors.affiliation: Department of Physiology, National Cheng Kung University Medical College, Tainan, Taiwan.
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Lai
authors.forename: Shainn-Wei
authors.initials: SW
authors.lastname: Wang
authors.forename: Lie
authors.initials: L
authors.lastname: Cheng
authors.forename: Woan-Yuh
authors.initials: WY
authors.lastname: Tarn
authors.forename: Shaw-Jenq
authors.initials: SJ
authors.lastname: Tsai
authors.forename: H Sunny
authors.initials: HS
authors.lastname: Sun
mesh_terms: D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D015696:Gene Products, tat / Q000378:metabolism*; D057809:HEK293 Cells; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*
chemical_list: D015696:Gene Products, tat; D012333:RNA, Messenger; D012367:RNA, Viral; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases