Activity of HIV-1 integrases recovered from subjects with varied rates of disease progression

We recently described 102 HIV-1 integrase sequences that were amplified fro m blood cells or plasma obtained up to 18 years ago from 5 hemophiliacs who later died of AIDS and 5 hemophiliacs subsequently classified as slow or n onprogressors (J Acquir Immune Defic Syndr Hum Retrovirol 1998;19:99-110). Although the region of the HIV-1 genome that encodes integrase was highly c onserved, none of the deduced protein sequences of the patient-derived enzy mes matched that of the clade B consensus or standard laboratory integrases . To test the hypothesis that the activity of HIV-1 integrases prevalent wi thin an infected person contributes to the rate of disease progression, we have now expressed and purified these proteins and compared them in various assays. Most of the 75 unique full-length integrase proteins from the 102 clones were enzymatically active. Comparison of proteins derived from sampl es obtained soon after infection showed that the specificity and extent of viral DNA processing and the amount of DNA joining (the two biologically re levant activities of integrase) did not differ between the two groups of pa tients. In addition, the relative usage of alternative nucleophiles for pro cessing and the amount of nonspecific nicking catalyzed by the proteins wer e indistinguishable between the patient groups. Although the patient-derive d enzymes often exhibited different patterns of target site preferences com pared with the laboratory integrase, there was no correlation with clinical course. Thus, the activities of HIV-1 integrases prevalent within these in fected individuals, at least as reflected by standard assays, did not influ ence or predict the rate of disease progression.