Genetic mechanisms underlying host susceptibility to central nervous system viral infections

PURPOSE OF REVIEW: To provide a critical review of the literature on the influence of host genetic variations on the susceptibility to viral encephalitis, and the proposed underlying key immunogenetic mechanisms. RECENT FINDINGS: Easier access to genomic sequencing has led to the identification of an ever-increasing number of monogenic defects and polymorphisms in genes that influence innate viral sensing, interferon signaling, cytotoxic lymphocyte function, antibody responses, cytokine regulation, and blood-brain barrier stability. While many of these genetic abnormalities have been implicated in neuroinvasion, severe or persistent viral infections, or inflammatory injury, the body of evidence supporting these possibilities is highly variable. We summarize each of the pathways in which these mutations have been described and discuss the evidence that supports their etiopathogenic role in viral encephalitis. SUMMARY: CNS viral infections may be predisposed to by specific vulnerabilities in immune homeostasis. Understanding convergent genetic mechanisms supports precision diagnostics, risk-stratification, and pathway-directed therapy.