title: HLA Class I and II alleles, heterozygosity and HLA-KIR interactions are associated with rates of genital HSV shedding and lesions.
abstract: Variation at HLA and KIR loci is associated with the severity of viral infections. To assess associations of genital HSV-2 infection with human HLA and KIR genetic loci, we measured the frequencies of genital herpes simplex virus (HSV) DNA detection and of genital lesions in HSV-2 seropositive persons. We followed 267 HSV-2 seropositive persons who collected daily genital swabs and recorded lesions for ⩾30 days. All persons were laboratory-documented as HIV-seronegative, and all were Caucasian by self-report. HSV detection rate and lesion frequency were compared by genotype using Poisson regression. Overall, HSV was detected on 19.1% of days and lesions on 11.6% of days. The presence of HLA-A*01 was directly associated with HSV detection frequency, whereas the presence of HLA-C*12 was inversely associated with HSV detection frequency. The presence of HLA-A*01 was directly associated with lesion rate, while HLA-A*26, -C*01 and -DQB1*0106 were associated with decreased lesions. We observed an interaction between the absence of both 2DS4del and HLA-Bw4 and higher lesion rate. Heterozygosity of HLA was also associated with reduced lesion frequency. Immune control of genital HSV infection relies on multiple interacting immunogenetic elements, including epistatic interactions between HLA and KIR.
authors.affiliation: Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle WA, USA.|Department of Biostatistics, University of Washington, Seattle WA, USA.|Department of Laboratory Medicine, University of Washington, Seattle WA, USA.
authors.forename: Amalia
authors.initials: A
authors.lastname: Magaret
authors.affiliation: Department of Medicine, University of Washington, Seattle WA, USA.
authors.forename: Lichun
authors.initials: L
authors.lastname: Dong
authors.affiliation: Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia 6150, Australia.|Department of Clinical Immunology, Royal Perth Hospital, Perth, Western Australia 6000, Australia.
authors.forename: Mina
authors.initials: M
authors.lastname: John
authors.affiliation: Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia 6150, Australia.|Department of Clinical Immunology, Royal Perth Hospital, Perth, Western Australia 6000, Australia.|Vanderbilt University, Nashville, TN, USA.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Mallal
authors.affiliation: Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia 6150, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: James
authors.affiliation: Westover Heights Clinic, Portland, OR, USA.
authors.forename: Terri
authors.initials: T
authors.lastname: Warren
authors.affiliation: Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia 6150, Australia.|Vanderbilt University, Nashville, TN, USA.|School of Anatomy, Physiology and Human Biology, University of Western Australia, Crawley, Western Australia 6009, Australia.
authors.forename: Silvana
authors.initials: S
authors.lastname: Gaudieri
authors.affiliation: Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle WA, USA.|Department of Laboratory Medicine, University of Washington, Seattle WA, USA.|Department of Medicine, University of Washington, Seattle WA, USA.|Department of Global Health, University of Washington, Seattle WA, USA.|Benaroya Research Institute, Seattle, WA, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Koelle
authors.affiliation: Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle WA, USA.|Department of Laboratory Medicine, University of Washington, Seattle WA, USA.|Department of Medicine, University of Washington, Seattle WA, USA.|Department of Epidemiology, University of Washington, Seattle WA, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Wald
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D005838:Genotype; D006558:Herpes Genitalis / Q000473:pathology / Q000821:virology*; D018258:Herpesvirus 2, Human / Q000502:physiology*; D006579:Heterozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D054340:Receptors, KIR / Q000378:metabolism*; D012008:Recurrence; D017201:Virus Shedding; D055815:Young Adult
chemical_list: D054340:Receptors, KIR