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

Jianhua Fang, Satoshi Kubota, Bin Yang, Naiming Zhou, Hui Zhang, Roseline Godbout, Roger J. Pomerantz

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117 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)471-480
Number of pages10
JournalVirology
Volume330
Issue number2
DOIs
Publication statusPublished - Dec 20 2004
Externally publishedYes

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Keywords

  • Co-factor
  • DDX1
  • DEAD Box
  • HIV-1
  • RNA Helicase
  • Rev

ASJC Scopus subject areas

  • Virology

Cite this

Fang, J., Kubota, S., Yang, B., Zhou, N., Zhang, H., Godbout, R., & Pomerantz, R. J. (2004). A DEAD box protein facilitates HIV-1 replication as a cellular co-factor of Rev. Virology, 330(2), 471-480. https://doi.org/10.1016/j.virol.2004.09.039