The roles of cellular factors in retroviral integration.
A key early step in the retroviral life cycle is the integration of reverse-transcribed viral cDNA into a chromosome of an infected cell. The key protein player in retroviral integration is the viral integrase, which enters the cell as part of the virus. Although purified integrase protein is necessary and sufficient to perform the basic catalytic DNA breakage and joining steps of retroviral integration, a variety of normal cellular proteins have been implicated as playing important roles in establishing the integrated provirus in cells. This chapter reviews the roles of host cell factors that function during integrase catalysis, during the repair of the resulting DNA recombination intermediate, and by potentially guiding viral preintegration complexes to their chromosomal locations for cDNA integration. The potential to interfere with proper integration by blocking either integrase catalysis or the function of cellular integration cofactors is also discussed.
Engelman
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Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. alan_engelman@dfci.harvard.edu
D000818:Animals; D004279:DNA, Viral / Q000235:genetics / Q000502:physiology; D006801:Humans; D019426:Integrases / Q000378:metabolism; D011133:Polysaccharide-Lyases / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics*; D016662:Virus Integration / Q000502:physiology*
D004279:DNA, Viral; D019426:Integrases; D011133:Polysaccharide-Lyases; C100002:hyaluronate lyase