HLA Class I and II alleles, heterozygosity and HLA-KIR interactions are associated with rates of genital HSV shedding and lesions

A. Magaret; L. Dong; M. John; S.A. Mallal; I. James; T. Warren; S. Gaudieri; D.M. Koelle; A. Wald

doi:10.1038/gene.2016.42

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HLA Class I and II alleles, heterozygosity and HLA-KIR interactions are associated with rates of genital HSV shedding and lesions

Journal article

Peer reviewed

HLA Class I and II alleles, heterozygosity and HLA-KIR interactions are associated with rates of genital HSV shedding and lesions

A. Magaret, L. Dong, M. John, S.A. Mallal, I. James, T. Warren, S. Gaudieri, D.M. Koelle and A. Wald

Genes and Immunity, Vol.17(7), pp.412-418

2016

DOI: https://doi.org/10.1038/gene.2016.42

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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.

Details

Title: HLA Class I and II alleles, heterozygosity and HLA-KIR interactions are associated with rates of genital HSV shedding and lesions
Authors/Creators: A. Magaret (Author/Creator) - Fred Hutch Cancer Center
L. Dong (Author/Creator) - University of Washington
M. John (Author/Creator) - Murdoch University
S.A. Mallal (Author/Creator) - Royal Perth Hospital
I. James (Author/Creator) - Murdoch University
T. Warren (Author/Creator) - Westover Heights Clinic
S. Gaudieri (Author/Creator) - School of Anatomy, Physiology and Human Biology
D.M. Koelle (Author/Creator) - Fred Hutch Cancer Center
A. Wald (Author/Creator) - Fred Hutch Cancer Center
Publication Details: Genes and Immunity, Vol.17(7), pp.412-418
Publisher: Nature Publishing Group
Identifiers: 991005543257907891
Copyright: © 2016 Macmillan Publishers Limited
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.161 Virology - Identification & Sequencing; 1.161.315 Herpesvirus Dynamics
Web Of Science research areas: Genetics & Heredity; Immunology
ESI research areas: Molecular Biology & Genetics