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J. Biol. Chem., Vol. 281, Issue 18, 12625-12635, May 5, 2006

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Association of RNA Helicase A with Human Immunodeficiency Virus Type 1 Particles^*

From the McGill AIDS Centre, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada H3T 1E2 and the Department of Medicine, McGill University, Montreal, Quebec H3A 2B4, Canada

RNA helicase A (RHA) belongs to the DEAH family of proteins that are capable of unwinding double-stranded RNA structure. In addition to its involvement in the metabolism of cellular RNA, RHA has been shown to stimulate RNA transcription from the long terminal repeat promoter of human immunodeficiency virus type 1 (HIV-1) as well as to enhance Rev/Rev response element-mediated gene expression. In this study, we provide evidence that RHA associates with HIV-1 Gag in an RNA-dependent manner. This interaction results in specific incorporation of RHA into HIV-1 particles. Knockdown of endogenous RHA in virus producer cells leads to generation of HIV-1 particles that are less infectious in part as a result of restricted reverse transcription. Therefore, RHA represents the first example of cellular RNA helicases that participate in HIV-1 particle production and promote viral reverse transcription.

Received for publication, September 27, 2005 , and in revised form, March 6, 2006.

^* This research was supported by grants from the Canadian Institutes of Health Research (CIHR), the Fonds de la Recherche en Sante du Quebec (FRSQ), and Canadian Foundation for AIDS Research. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Lady Davis Institute, Rm. 326, Jewish General Hospital, 3755 Cote Ste. Catherine, Montreal, Quebec H3T 1E2, Canada. Tel.: 514-340-8260; Fax: 514-340-7537; E-mail: chen.liang{at}mcgill.ca.

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