In Vivo Analysis of Retroviral Integrase Structure and Function

There are two retroviral integration loci. One encodes the transacting IN protein, which is cleaved from the carboxyl terminus of the Gag-Pol polyprotein precursor during virus assembly. The second locus is the cis-acting attachment (att) site, comprising the terminal sequences at the U3 and U5 ends of linear viral cDNA. Integrase and att site mutant viruses can be blocked at different steps of the viral replication cycle. Class I IN mutants are blocked specifically at the integration step. Class II IN mutants, on the other hand, display pleiotropic defects, most notably in virion morphogenesis and/or reverse transcription. Mutations in the U5 end att site can also disrupt reverse transcription in addition to integration. It is prudent to use caution when interpreting results of in vivo mutagenesis experiments that target retroviral IN and the att site.