FIRST REPORT OF A HEALTHY INDIAN HETEROZYGOUS FOR DELTA-32 MUTANT OF HIV-1 CO-RECEPTOR-CCR5 GENE

The beta-chemokine receptor, CCR5, is a major co-receptor for macropha ge tropic non-syncytia-inducing isolates of HIV-1. Recently a 32 bp ho mozygous deletion in the coding region of CCR5 has been reported in a very small percentage (< 1 %) of Caucasian individuals who remain unin fected, despite multiple exposure to the wild-type virus. This mutant allele in the heterozygous form (CCR5/32 ccr5) was readily detected in a normal unrelated Caucasian population of European heritage with var ying frequencies (13 - 20 %). However, when a large number of the non- Caucasian population (261 Africans and 423 Asians) were screened for t he presence of this deleted allele, not a single case of either homozy gous or heterozygous mutant for Delta 32 allele of CCR5 was detected. We screened 100 normal individuals and found a single heterozygous cas e with an identical 32 bp deletion in CCR5 gene reported earlier, the rest possessed wild-type alleles. This deleted gene was inherited in M endelian fashion among the family members of this individual. Thus, th e frequency of this deleted allele in India among unrelated normal ind ividuals is likely to be very low (< 1 %). We observed a moderate tran sdominant effect of this mutant allele in a fusion assay. Finally, we show a significant inhibition of fusion of cell membranes when the 176 -bp region of CCR5 was used as an antisense. (C) 1998 Elsevier Science B.V.