Journal
GENES AND IMMUNITY
Volume 10, Issue 7, Pages 662-666Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/gene.2009.50
Keywords
MTHFR; folate metabolism; cytomegalovirus; mouse models; innate resistance
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Funding
- Canadian Institutes of Health Research [MOP-7781, MOP-4232]
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Folates provide one-carbon units for nucleotide synthesis and methylation reactions. A common polymorphism in the MTHFR gene (677C-T) results in reduced enzymatic activity, and is associated with an increased risk for neural tube defects and cardiovascular disease. The high prevalence of this polymorphism suggests that it may have experienced a selective advantage under environmental pressure, possibly an infectious agent. To test the hypothesis that methylenetetrahydrofolate reductase (MTHFR) genotype influences the outcome of infectious disease, we examined the response of Mthfr-deficient mice against mouse cytomegalovirus (MCMV) infection. Acute MCMV infection of Mthfr(-/-) mice resulted in early control of cytokine secretion, decreased viral titer and preservation of spleen immune cells, in contrast to Mthfr wild-type littermates. The phenotype was abolished in MTHFR transgenic mice carrying an extra copy of the gene. Infection of primary fibroblasts with MCMV showed a decrease in viral replication and in the number of productively infected cells in Mthfr(+/-) fibroblasts compared with wild-type cells. These results indicate that Mthfr deficiency protects against MCMV infection in vivo and in vitro, suggesting that human genetic variants may provide an advantage in the host response against certain pathogens. Genes and Immunity (2009) 10, 662-666; doi:10.1038/gene.2009.50; published online 16 July 2009
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