Functional MxA promoter polymorphism associated with subacute sclerosing panencephalitis.

Abstract

The antivirally active MxA protein is induced by interferon (IFN) alpha/beta and inhibits the replication of single-stranded RNA viruses including measles virus (MV). The authors investigated whether the MxA gene contributed to the development of subacute sclerosing panencephalitis (SSPE) in Japanese individuals. Single-nucleotide polymorphisms (SNP) in the promoter region of the MxA gene were screened, association studies were performed between two SNP and SSPE, and then a functional difference in the promoter activities of the two SNP was investigated by a dual luciferase reporter assay. Four SNP were found (-88 G/T, -123 C/A, -200 T/C, and -213 G/T), and SSPE patients exhibited a higher frequency of both the -88T allele and the -88TT genotype than controls (p = 0.040 and 0.003). The IFN-induced up-regulation of the MxA promoter activity of the sequence with -88T was found to be significantly higher than that with G. MxA promoter -88 G/T SNP may confer host genetic susceptibility to SSPE in Japanese individuals. The finding that homozygotes of the MxA -88T allele with a high MxA-producing capability were more frequently seen in SSPE patients suggests that the MxA protein promotes the establishment of persistent MV infection of neural cells.