International Journal of Medical Laboratory

Inborn errors of immunity (IEI) are heterogeneous genetic disorders that are susceptible to frequent bacterial, fungal, and viral infections. Herpes simplex virus type 1, 2 (HSV1, 2) is the most common and important cause of viral encephalitis. Innate and acquired immunity have a central role in controlling HSV infection. There is incomplete evidence about the increased susceptibility to herpes simplex encephalitis (HSE) in HSV-infected patients. Studies strongly suggest that HSE has a genetic susceptibility at least in some people. Several studies have shown that defects in the Toll-like Receptor (TLR)3 signaling and interferon (IFN) production and IFN-independent cell-intrinsic mechanisms contribute to HSE. We searched the Web of Science, PubMed, Scopus, and Google Scholar databases to select the latest and most reliable papers and articles published in English and Persian. In the present review, we discuss IEI and genetic abnormalities that predispose individuals to HSE. Genetic defects in components of the TLR3 signaling pathway, such as TLR3, UNC93B1, TRIF, TRAF3, IRF3, and Signal transducer and activator of transcription 1 (STAT1), have been reported as responsible genes for HSE. Other genetic mutations have also been found as the etiology of HSE in some people. Despite HSE being a rare complication of HSV, genetic evaluation of these patients can diagnose some IEI and may give us new insights for future investigations in the fields of diagnosis, treatment, and prophylaxis.