A DEAD box protein facilitates HIV-1 replication as a cellular co-factor of Rev

Virology. 2004 Dec 20;330(2):471-80. doi: 10.1016/j.virol.2004.09.039.


HIV-1 Rev escorts unspliced viral mRNAs out of the nucleus of infected cells, which allows formation of infectious HIV-1 virions. We have identified a putative DEAD box (Asp-Glu-Ala-Asp) RNA helicase, DDX1, as a cellular co-factor of Rev, through yeast and mammalian two-hybrid systems using the N-terminal motif of Rev as "bait". DDX1 is not a functional homolog of HIV-1 Rev, but down-regulation of DDX1 resulted in an alternative splicing pattern of Rev-responsive element (RRE)-containing mRNA, and attenuation of Gag p24 antigen production from HLfb rev- cells rescued by exogenous Rev. Co-transfection of a DDX1 expression vector with HIV-1 significantly increased viral production. DDX1 binding to Rev, as well as to the RRE, strongly suggest that DDX1 affects Rev function through the Rev-RRE axis. Moreover, down-regulation of DDX1 altered the steady state subcellular distribution of Rev, from nuclear/nucleolar to cytoplasmic dominance. These findings indicate that DDX1 is a critical cellular co-factor for Rev function, which maintains the proper subcellular distribution of this lentiviral regulatory protein. Therefore, alterations in DDX1-Rev interactions could induce HIV-1 persistence and targeting DDX1 may lead to rationally designed and novel anti-HIV-1 strategies and therapeutics.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Chlorocebus aethiops
  • DEAD-box RNA Helicases
  • Gene Expression Regulation, Viral*
  • Gene Products, rev / metabolism*
  • Genes, env / physiology
  • HIV Core Protein p24 / biosynthesis
  • HIV-1 / physiology*
  • Humans
  • Protein Binding
  • Protein Interaction Mapping
  • RNA Helicases / metabolism*
  • RNA Splicing
  • RNA, Viral / metabolism
  • Two-Hybrid System Techniques
  • Virus Replication* / genetics
  • rev Gene Products, Human Immunodeficiency Virus


  • Gene Products, rev
  • HIV Core Protein p24
  • RNA, Viral
  • rev Gene Products, Human Immunodeficiency Virus
  • DDX1 protein, human
  • DEAD-box RNA Helicases
  • RNA Helicases