Nucleoprotein Intermediates in HIV-1 DNA Integration: Structure and Function of HIV-1 Intasomes
Integration of a DNA copy of the viral genome into host DNA is an essential step in the replication cycle of HIV-1 and other retroviruses and is an important therapeutic target for drugs. DNA integration is catalyzed by the viral integrase protein and proceeds through a series of stable nucleoprotein complexes of integrase, viral DNA ends and target DNA. These nucleoprotein complexes are collectively called intasomes. Retroviral intasomes undergo a series of transitions between initial formation and catalysis of the DNA cutting and joining steps of DNA integration. Intasomes, rather than free integrase protein, are the target of currently approved drugs that target HIV-1 DNA integration. High-resolution structures of HIV-1 intasomes are needed to understand their detailed mechanism of action and how HIV-1 may escape by developing resistance. Here, we focus on our current knowledge of the structure and function of HIV-1 intasomes, with reference to related systems as required to put this knowledge in context.
KeywordsHIV-1 DNA integration Genome Nucleoprotein intermediates Retroviruses Retrotransposons Transposons
We thank Alan Engelman and Wei Yang for valuable input to the manuscript. This work was supported by the Intramural Program of the National Institute of Diabetes and Digestive Diseases of the National Institutes of Health and by the Intramural AIDS Targeted Antiviral Program of the Office of the Director of the NIH.
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