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Abstract
Background: The antivirally active MxA protein is induced by interferon (IFN) α/β 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.
Methods: 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.
Results: 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.
Conclusions: 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.
- Received July 11, 2003.
- Accepted October 15, 2003.
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