The integration of viral cDNA into the host genome is a key step in the life cycle of retroviruses. In Cell Host and Microbe, Cereseto and colleagues identify a host restriction factor that interferes with the integration of human immunodeficiency virus type 1 (HIV-1). Retroviral integration requires a viral integrase whose activity is enhanced by host acetylases. A screen of host proteins that interact with acetylated viral integrase identifies KAP1 (TRIM28) of the transmembrane adaptor TRIM family. KAP1 inhibits integration of and infection with HIV-1, and it seems to do this by forming a complex with the deacetylase HDAC1 and binding to integrase targets. Once bound to integrase, the KAP1-HDAC1 complex deacetylates it and thereby decreases its activity and ability to facilitate viral integration. The function of KAP1 seems to be wholly dependent on deacetylation, as it is ineffective in the absence of HDAC1, even if KAP1 is overexpressed. This study extends the family of factors able to restrict viral infection and identifies an important step in the viral life cycle at which they may act.

Cell Host Microbe 9, 484–495 (2011)