hiv-1 integrase-dna recognition mechanismshiv - 1 integrase-dna识别机制.pdfVIP

Viruses 2009, 1, 713-736; doi:10.3390/v1030713 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review HIV-1 Integrase-DNA Recognition Mechanisms Jacques J. Kessl, Christopher J. McKee, Jocelyn O. Eidahl, Nikolozi Shkriabai, Ari Katz and Mamuka Kvaratskhelia * Center for Retrovirus Research and Comprehensive Cancer Center, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA; E-Mails: kessl.1@ (J.J.K.); mckee.473@ (C.J.M.); eidahl.1@ (J.O.E.), shkriabai.1@ (N.S.); katz.147@ (A.K.) * Author to whom correspondence should be addressed; E-Mail: kvaratskhelia.1@; Tel.: +1-614-292-6091; Fax: +1-614-292-7766. Received: 30 September 2009; in revised form: 3 November 2009 / Accepted: 4 November 2009 / Published: 5 November 2009 Abstract: Integration of a reverse transcribed DNA copy of the HIV viral genome into the host chromosome is essential for virus replication. This process is catalyzed by the virally encoded protein integrase. The catalytic activities, which involve DNA cutting and joining steps, have been recapitulated in vitro using recombinant integrase and synthetic DNA substrates. Biochemical and biophysical studies of these model reactions have been pivotal in advancing our understanding of mechanistic details for how IN interacts with viral and target DNAs, and are the focus of the present review. Keywords: HIV; retroviruses; DNA; integrase; crosslinking; footprinting 1. Introduction HIV-1 integrase (IN) catalyses integration of the reverse transcribed DNA copy of the viral g