High frequency of G to A transition mutation in the stromal cell derived factor-1 gene in India, a chemokine that blocks HIV-1 (X4) infection: multiple proteins bind to 3'-untranslated region of SDF-1 RNA.

It has become clear that mutations in a variety of host genes possess the ability to influence the progression of HIV-1, prominent among them are the chemokines. Stromal cell derived factor-1 (SDF-1), an alpha-chemokine, is a natural ligand for HIV-1 coreceptor-CXCR4 and a potent chemokine that blocks infection by X4 viruses. Nucleotide G to A transition (nucleotide position 801 with respect to the ATG initiation codon) in the 3'-untranslated region of SDF-1 RNA is implicated in having disease-modifying effects. We have screened 100 normal healthy individuals from north India where HIV-1 is spreading at an alarming rate. This mutation is present in 40% (40 out of 100) individuals, 32% being heterozygous and 8% being homozygous for this mutation. This mutation showed Mendelian inheritance in one of the families studied. This observation could be important in understanding the progression or pathogenesis of HIV-1 in India. We also show that multiple proteins bind in the 3'-untranslated region of the SDF-1 RNA.