Abstract
Herpes simplex virus type 1 (HSV-1) is a neurotropic virus linked to a range of acute and chronic neurological disorders affecting distinct regions of the brain. Unusually, HSV-1 entry into cells requires the interaction of viral proteins glycoprotein D (gD) and glycoprotein B (gB) with distinct cellular receptor proteins. Several different gD and gB receptors have been identified, including TNFRSF14/HVEM and PVRL1/nectin 1 as gD receptors and PILRA, MAG, and MYH9 as gB receptors. We investigated the expression of these receptor molecules in different areas of the adult and developing human brain using online transcriptome databases. Whereas all HSV-1 receptors showed distinct expression patterns in different brain areas, the Allan Brain Atlas (ABA) reported increased expression of both gD and gB receptors in the hippocampus. Specifically, for PVRL1, TNFRFS14, and MYH9, the differential z scores for hippocampal expression, a measure of relative levels of increased expression, rose to 2.9, 2.9, and 2.5, respectively, comparable to the z score for the archetypical hippocampus-enriched mineralocorticoid receptor (NR3C2, z = 3.1). These data were confirmed at the Human Brain Transcriptome (HBT) database, but HBT data indicate that MAG expression is also enriched in hippocampus. The HBT database allowed the developmental pattern of expression to be investigated; we report that all HSV1 receptors markedly increase in expression levels between gestation and the postnatal/adult periods. These results suggest that differential receptor expression levels of several HSV-1 gD and gB receptors in the adult hippocampus are likely to underlie the susceptibility of this brain region to HSV-1 infection.
Highlights
Infection with herpes simplex virus type 1 and 2 (HSV-1/2) causes orofacial, genital, cerebral, and ocular disorders
Herpes simplex virus type 1 (HSV-1) is unusual among viruses in that it requires the expression of two different receptors on the same target cell, which respectively interact with viral glycoproteins glycoprotein B (gB) and glycoprotein D (gD) (BIntroduction^ section)
We present for the first time a systematic analysis of the distribution of both gB and gD HSV-1 receptors in human brain
Summary
Infection with herpes simplex virus type 1 and 2 (HSV-1/2) causes orofacial, genital, cerebral, and ocular disorders. HSV-1 has been implicated in diverse acute and chronic neurological diseases including meningitis, encephalitis, and epilepsy (Gilden et al 2007; KleinschmidtDeMasters and Gilden 2001). HSV meningitis typically affects the temporal cortex, and infection of the limbic system including the hippocampus (Hpc) is implicated in HSV-1 encephalitis (Damasio and Van Hoesen 1985). Epilepsy associated with HSV-1 may involve the Hpc because origins of focal epilepsy are typically found in the temporal lobe (reviewed in Blair 2012). An immunological study reported the presence of HSV antigen within temporal lobe and Hpc of human herpes encephalitis, with further evidence for antigen in amygdala and olfactory cortex (Esiri 1982). The tropism of HSV for the temporal brain remains unexplained
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