Lys-34, Dispensable for Integrase Catalysis, Is Required for Preintegration Complex Function and Human Immunodeficiency Virus Type 1 Replication
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CitationLu, R., N. Vandegraaff, P. Cherepanov, and A. Engelman. 2005. “Lys-34, Dispensable for Integrase Catalysis, Is Required for Preintegration Complex Function and Human Immunodeficiency Virus Type 1 Replication.” Journal of Virology 79 (19): 12584–91. https://doi.org/10.1128/jvi.79.19.12584-12591.2005.
AbstractRetroviral integrases (INs) function in the context of preintegration complexes (PICs). Two conserved Lys residues in the N-terminal domain of human immunodeficiency virus type 1 (HIV-1) IN were analyzed here for their roles in integration and virus replication. Whereas HIV-1(K46A) grew like the wild type, HIV-1(K34A) was dead. Yet recombinant INK34A protein functioned in in vitro integration assays, and Vpr-INK34A efficiently transcomplemented the infectivity defect of an IN active site mutant virus in cells. HIV-1(K34A) was therefore similar to a number of previously characterized mutant viruses that failed to replicate despite encoding catalytically competent IN. To directly analyze mutant PIC function, a sensitive PCR-based integration assay was developed. HIV-1(K34A) and related mutants failed to support detectable levels (< 1% of wild type) of integration. We therefore concluded that mutations like K34A disrupted higher-order interactions important for PIC function/maturation compared to the innate catalytic activity of IN enzyme.
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