TY - JOUR
T1 - A DEAD box protein facilitates HIV-1 replication as a cellular co-factor of Rev
AU - Fang, Jianhua
AU - Kubota, Satoshi
AU - Yang, Bin
AU - Zhou, Naiming
AU - Zhang, Hui
AU - Godbout, Roseline
AU - Pomerantz, Roger J.
N1 - Funding Information:
The authors thank the AIDS Reagent Program, Division of AIDS, NIAID, NIH, for providing the HLfb rev(−) line that was donated by Drs. Barabara Felber and George Pavlakis; Dr. Tristram G. Parslow for the pDM128 construct, Dr. Michael H. Malim for pcRev, Dr. Bryan R. Cullen for providing a rabbit anti-Rev antibody, and Dr. Keyang Chen and Ms. Chune Zhang for helpful suggestions and technical assistance. We also thank Ms. Rita M. Victor and Ms. Brenda O. Gordon for excellent secretarial assistance. This work was supported in part by US PHS grants AI43876, AI43289, NS41864 and NS27405 to R.J.P.
PY - 2004/12/20
Y1 - 2004/12/20
N2 - 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.
AB - 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.
KW - Co-factor
KW - DDX1
KW - DEAD Box
KW - HIV-1
KW - RNA Helicase
KW - Rev
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U2 - 10.1016/j.virol.2004.09.039
DO - 10.1016/j.virol.2004.09.039
M3 - Article
C2 - 15567440
AN - SCOPUS:9644289433
VL - 330
SP - 471
EP - 480
JO - Virology
JF - Virology
SN - 0042-6822
IS - 2
ER -