HLA polymorphisms and detection of kaposi sarcoma-associated herpesvirus DNA in saliva and peripheral blood among children and their mothers in the uganda sickle cell anemia KSHV Study

Mercy Guech-Ongey,Britta Eiz-Vesper,Kishor Bhatia,Constança Figueiredo,Christopher M Ndugwa,Ruth M Pfeiffer,Thomas F Schulz,Sam M Mbulaiteye,Murielle Verboom,Paul M Bakaki,Anchilla M Owor,Rainer Blasczyk

doi:10.1186/1750-9378-5-21

Abstract

Kaposi sarcoma-associated herpesvirus (KSHV, also called Human herpesvirus 8 or HHV8) is a γ-2 herpesvirus that causes Kaposi sarcoma. KSHV seroprevalence rates vary geographically with variable rates recorded in different sub Sahara African countries, suggesting that effects of genetic and/or environmental factors may influence the risk of infection. One study conducted in South Africa, where KSHV seroprevalence is relatively low, found that carriage of human leukocyte antigen (HLA) alleles HLA-A*6801, HLA-A*30, HLA-A*4301, and HLA-DRB1*04 was associated with increased shedding of KSHV DNA in saliva. Confirmation of those results would strengthen the hypothesis that genetic factors may influence KSHV distribution by modulating KSHV shedding in saliva. To explore these associations in another setting, we used high resolution HLA-A, B, and DRB1 typing on residual samples from the Uganda Sickle Cell Anemia KSHV study, conducted in a high KSHV seroprevalence region, to investigate associations between HLA and KSHV shedding in saliva or peripheral blood among 233 children and their mothers. HLA-A and HLA-DRB1 alleles were not associated with KSHV shedding in our study, but our study was small and was not adequately powered to exclude small associations. In exploratory analyses, we found marginal association of KSHV DNA shedding in saliva but not in peripheral blood among children carrying HLA- B*4415 and marginal association of KSHV DNA shedding in peripheral blood but not in saliva among children carrying HLA- B*0801 alleles. The contribution of individual HLA polymorphisms to KSHV shedding is important but it may vary in different populations. Larger population-based studies are needed to estimate the magnitude and direction of association of HLA with KSHV shedding and viral control.

Highlights

Kaposi sarcoma-associated herpesvirus (KSHV, called Human herpesvirus 8 or human herpesvirus 8 (HHV8)) is a g-2 herpesvirus etiologically linked to Kaposi sarcoma (KS) [1]
A study in South Africa found increased Kaposi’s sarcoma-associated herpesvirus (KSHV) DNA shedding in saliva among subjects carrying human leukocyte antigens (HLA) HLA-A*6801, HLAA*30, HLA-A*4301, and HLA-DRB1*04 alleles [8]
We sought to replicate the findings from South Africa in Uganda and to explore novel HLA allele associations with KSHV shedding using residual samples and data from the Uganda Sickle Cell Anemia KSHV study [12]

Summary

Introduction

A study in South Africa found increased KSHV DNA shedding in saliva among subjects carrying human leukocyte antigens (HLA) HLA-A*6801, HLAA*30, HLA-A*4301, and HLA-DRB1*04 alleles [8]. We sought to replicate the findings from South Africa in Uganda and to explore novel HLA allele associations with KSHV shedding using residual samples and data from the Uganda Sickle Cell Anemia KSHV study [12]. We performed high-resolution HLA-A, -B and -DRB1 typing on residual DNA obtained from saliva or buffy coat of the children and their mothers from the KSHV viral study.

Results

Conclusion