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HIV Integrase, a Brief Overview from Chemistry to Therapeutics*

R. Craigie

Published 2001 in Journal of Biological Chemistry

ABSTRACT

Retroviruses are a large and diverse family of RNA viruses that synthesize a DNA copy of their RNA genome after infection of the host cell. Integration of this viral DNA into host DNA is an essential step in the replication cycle of HIV and other retroviruses (reviewed in Refs. 1–3). The integrated viral DNA is transcribed to make the RNA genome of progeny virions and the template for translation of viral proteins. Following assembly, virions bud from the cell surface and subsequently infect previously uninfected cells, thus completing the replication cycle. An infecting retrovirus introduces a large nucleoprotein complex into the cytoplasm of the host cell. This complex, which is derived from the core of the infecting virion, contains two copies of the viral RNA together with a number of viral proteins, including reverse transcriptase and integrase. Reverse transcription of the viral RNA occurs within the complex to make a double-stranded DNA copy of the viral genome, the viral DNA substrate for integration. The viral DNA remains associated with both viral and cellular proteins in a nucleoprotein complex termed the preintegration complex. One constituent of the preintegration complex is the viral integrase protein, the key player in the integration of the viral DNA into the host genome. The other components of the preintegration complex that are transported to the nucleus along with the viral DNA and integrase, and their possible functions, have not been firmly established and are not discussed here. The critical DNA cutting and joining events that integrate the viral DNA are carried out by the integrase protein itself. Here we review our current knowledge of the molecular mechanism of this reaction and discuss some of the key issues that are yet to be understood.

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