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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

Genes & Immunity volume 17, pages 412–418 (2016)Cite this article

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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.

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Acknowledgements

We thank the participants and the contributing labs, including the University of Washington Clinical Virology lab for HSV Western Blots and HIV serology, the University of Washington Molecular Virology lab for HSV PCR, and the Koelle lab for specimen handling. We are also grateful to Stacy Selke at the Virology Research Clinic for managing and compiling the subsequent clinical and laboratory results. The work was funded by NIH grants P01AI030731 and R01AI094019.

Author information

Author notes

  1. D M Koelle and A Wald: These authors contributed equally to this work.

Authors and Affiliations

  1. Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    A Magaret, D M Koelle & A Wald

  2. Department of Biostatistics, University of Washington, Seattle, WA, USA

    A Magaret

  3. Department of Laboratory Medicine, University of Washington, Seattle, WA, USA

    A Magaret, D M Koelle & A Wald

  4. Department of Medicine, University of Washington, Seattle, WA, USA

    L Dong, D M Koelle & A Wald

  5. Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Australia

    M John, S A Mallal, I James & S Gaudieri

  6. Department of Clinical Immunology, Royal Perth Hospital, Perth, Australia

    M John & S A Mallal

  7. Department of Medicine, Vanderbilt University, Nashville, TN, USA

    S A Mallal & S Gaudieri

  8. Westover Heights Clinic, Portland, OR, USA

    T Warren

  9. School of Anatomy, Physiology and Human Biology, University of Western Australia, Crawley, Australia

    S Gaudieri

  10. Department of Global Health, University of Washington, Seattle, WA, USA

    D M Koelle

  11. Department of Epidemiology, University of Washington, Seattle, WA, USA

    D M Koelle & A Wald

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  1. A Magaret
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Correspondence to D M Koelle.

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Competing interests

ASM is a consultant for AiCuris and Immune Design. DMK is co-inventor on patents concerning HSV-2 vaccine candidates that stimulate T-cell responses, receives contract funding from Sanofi Pasteur, Merck, Immune Design, and Admedus, and is a consultant to EISAI, Inc. AW is co-inventor on patents concerning HSV-2 vaccine candidates that stimulate T-cell responses, receives grant funding from NIH, clinical trial contracts from Genocea and Vical and is a consultant for AiCuris, and GSK. The remaining authors declare no conflict of interest.

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Magaret, A., Dong, L., John, M. et al. HLA Class I and II alleles, heterozygosity and HLA-KIR interactions are associated with rates of genital HSV shedding and lesions. Genes Immun 17, 412–418 (2016). https://doi.org/10.1038/gene.2016.42

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