title: Host genetic factors in susceptibility to herpes simplex type 1 virus infection: contribution of polymorphic genes at the interface of innate and adaptive immunity.
abstract: HSV-1 establishes life-long latency that can result in clinical relapses or in asymptomatic virus shedding. Although virtually all adults have been exposed to HSV-1, the clinical course varies remarkably. Genetic host variability could be related to this clinical diversity. In this study, we analyzed the contribution of gene families in chromosomes 1, 6, 12, and 19, which encode key regulators of the innate and adaptive immunity, in a cohort of 302 individuals. Class I and class II alleles of the HLA system, the copy-number variation of NK cell receptor genes (KIR and NKG2C), the combinations of killer cell Ig-like receptor and their HLA ligands, and CD16A and CD32A allotypes of variable affinity for IgG subclasses were all studied. Although no major susceptibility locus for HSV-1 was identified, our results show that the risk of suffering clinical HSV-1 infection is modified by MHC class I allotypes (B*18, C*15, and the group of alleles encoding A19), the high-affinity receptor/ligand pair KIR2DL2/HLA-C1, and the CD16A-158V/F dimorphism. Conversely, HLA class II and CD32A polymorphisms and NKG2C deletion did not seem to influence the clinical course of herpetic infection. Collectively, these findings support an important role in host defense against herpetic infection for several polymorphic genes implicated in adaptive immunity and in surveillance of its subversion. They confirm the crucial role of cytotoxic cells (CTL and NK) and the contribution of genetic diversity to the clinical course of HSV-1 infection.
authors.affiliation: Laboratorio de Inmunogenética-HLA, Hospital Universitario Puerta de Hierro, Majadahonda 28220, Spain.
authors.forename: Manuela
authors.initials: M
authors.lastname: Moraru
authors.forename: Elisa
authors.initials: E
authors.lastname: Cisneros
authors.forename: Natalia
authors.initials: N
authors.lastname: Gómez-Lozano
authors.forename: Rosario
authors.initials: R
authors.lastname: de Pablo
authors.forename: Francisca
authors.initials: F
authors.lastname: Portero
authors.forename: María
authors.initials: M
authors.lastname: Cañizares
authors.forename: Mercedes
authors.initials: M
authors.lastname: Vaquero
authors.forename: Gastón
authors.initials: G
authors.lastname: Roustán
authors.forename: Isabel
authors.initials: I
authors.lastname: Millán
authors.forename: Miguel
authors.initials: M
authors.lastname: López-Botet
authors.forename: Carlos
authors.initials: C
authors.lastname: Vilches
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics*; D000328:Adult; D002877:Chromosomes, Human / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D015236:HLA-C Antigens / Q000235:genetics / Q000276:immunology; D006561:Herpes Simplex / Q000235:genetics* / Q000276:immunology; D018259:Herpesvirus 1, Human; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D007157:Immunologic Surveillance / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology; D054343:Receptors, KIR2DL2 / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: C496124:FCGR3A protein, human; D015236:HLA-C Antigens; C515077:KIR2DL2 protein, human; D017452:Receptors, IgG; D054343:Receptors, KIR2DL2