CXCR4 AND CCR5 GENETIC POLYMORPHISMS IN LONG-TERM NONPROGRESSIVE HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION - LACK OF ASSOCIATION WITH MUTATIONS OTHER THAN CCR5-DELTA-32

Polymorphisms in the coding sequences of CCR5 and CXCR4 were studied i n a group of human immunodeficiency virus (HIV)-infected long-term non progressors. Two different point mutations were found in the CXCR4 cod ing sequence. One of these CXCR4 mutations was silent, and each was un ique to two nonprogressors. The well described 32-bp deletion within t he CCR5 coding sequence (CCR5-Delta 32) was found in 4 of 13 nonprogre ssors, and 12 different point mutations were found scattered over the CCR5 coding sequence from 8 nonprogressors. Most of the mutations crea ted either silent or conservative changes in the predicted amino acid sequence: only one of these mutations was found in more than a single nonprogressor. All nonsilent mutations were tested in an HIV envelope- dependent fusion assay, and all functioned comparably to wild-type con trols. Polymorphisms in the CXCR4 and CCR5 coding sequences other than CCR5-Delta 32 do not appear to play a dominant mechanistic role in no nprogression among HIV-infected individuals.