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Significance Infection with human cytomegalovirus (HCMV) is a growing health problem, creating diagnostic and therapeutic challenges. Biomarkers for risk of infection are lacking, and the limited drugs that inhibit HCMV have major side effects. New strategies for virus control are needed. We report on the role of nucleotide-binding oligomerization domain 1 (NOD1), a cytoplasmic pattern recognition receptor, in HCMV suppression. NOD1 activation (through IKKα and IRF3) resulted in IFN response and HCMV inhibition. Specific mutations in NOD1 showed differential effects on HCMV replication in vitro. In a nested study of HCMV vaccine, specific polymorphisms in NOD1 were detected in HCMV-infected women compared with noninfected women. Our work provides direction for studies of innate immune response to HCMV and genetic susceptibility through NOD1.

Role of nucleotide-binding oligomerization domain 1 (NOD1) and its variants in human cytomegalovirus control in vitro and in vivo