title: Distribution of cellular HSV-1 receptor expression in human brain.
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.
authors.affiliation: Division of Infection and Pathway Medicine, University of Edinburgh, 49 Little France Crescent, Edinburgh, EH16 4SB, UK. richardlathe@ed.ac.uk.
authors.forename: Richard
authors.initials: R
authors.lastname: Lathe
authors.affiliation: Division of Infection and Pathway Medicine, University of Edinburgh, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
authors.forename: Juergen G
authors.initials: JG
authors.lastname: Haas
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism* / Q000821:virology; D001931:Brain Mapping; D002675:Child, Preschool; D030541:Databases, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015967:Gene Expression Regulation, Viral; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D020409:Molecular Motor Proteins / Q000235:genetics / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D000075983:Nectins / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics* / Q000378:metabolism*; D059467:Transcriptome; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C115082:MAG protein, human; C103814:MYH9 protein, human; D008562:Membrane Glycoproteins; D020409:Molecular Motor Proteins; D018992:Myelin-Associated Glycoprotein; C000619010:NECTIN1 protein, human; D000075983:Nectins; C412263:PILRA protein, human; D011971:Receptors, Immunologic; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; C506028:TNFRSF14 protein, human; D014759:Viral Envelope Proteins; C562160:glycoprotein B, human herpesvirus 1; C039447:glycoprotein D, Human herpesvirus 1; C049545:simplexvirus receptor; D018995:Myosin Heavy Chains
keywords: Brain; Glycoprotein B; Glycoprotein D; HSV-1; Hippocampus; MAG; MYH9; PILRA; PVRL1/nectin 1; TNFRSF14/HVEM; Virus receptor