HLA-DQ β1 alleles associated with Epstein-Barr virus (EBV) infectivity and EBV gp42 binding to cells

Li, Qingxue; Bu, Wei; Gabriel, Erin E.; Aguilar, Fiona; Hoshino, Yo; Miyadera, Haruo; Hess, Christoph; Hornung, Ronald L.; Roy, Amitava; Cohen, Jeffrey I.

doi:10.1172/jci.insight.85687

Cited by 10 publications

(11 citation statements)

References 42 publications

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“…However, EBV infection of individuals with non-permissive HLA-DQ allotypes could conceivably proceed through other class II HLA molecules. Consistent with these molecular differences, HLA-DQB1*02 allotypes are associated with gp42 binding and increased EBV seropositivity whereas HLA-DQB1*03, *04, *05, and *06 alleles associate with lack of seroconversion and less strong binding affinity (Li et al 2017). Following infection, gp42 is repurposed as an HLA class II evasion protein to dampen the CD4 + T cell response (Ressing et al 2003).…”

Section: Hla Alleles and Their Receptors Coordinate Variable Immune R...mentioning

confidence: 94%

The impact of HLA polymorphism on herpesvirus infection and disease

Palmer¹,

Norman²

2023

Immunogenetics

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Human Leukocyte Antigens (HLA) are cell surface molecules, central in coordinating innate and adaptive immune responses, that are targets of strong diversifying natural selection by pathogens. Of these pathogens, human herpesviruses have a uniquely ancient relationship with our species, where coevolution likely has reciprocating impact on HLA and viral genomic diversity. Consistent with this notion, genetic variation at multiple HLA loci is strongly associated with modulating immunity to herpesvirus infection. Here, we synthesize published genetic associations of HLA with herpesvirus infection and disease, both from case/control and genome-wide association studies. We analyze genetic associations across the eight human herpesviruses and identify HLA alleles that are associated with diverse herpesvirus-related phenotypes. We find that whereas most HLA genetic associations are virus- or disease-specific, HLA-A*01 and HLA-A*02 allotypes may be more generally associated with immune susceptibility and control, respectively, across multiple herpesviruses. Connecting genetic association data with functional corroboration, we discuss mechanisms by which diverse HLA and cognate receptor allotypes direct variable immune responses during herpesvirus infection and pathogenesis. Together, this review examines the complexity of HLA-herpesvirus interactions driven by differential T cell and Natural Killer cell immune responses.

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Section: Hla Alleles and Their Receptors Coordinate Variable Immune R...mentioning

confidence: 94%

The impact of HLA polymorphism on herpesvirus infection and disease

Palmer¹,

Norman²

2023

Immunogenetics

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“…This small number of studies may be a consequence of the low frequency of EBV seronegative individuals in the adult population meaning large cohorts are required to identify sufficient EBV seronegative donors to produce robust conclusions. All three genes identified as being associated with EBV serostatus (mannose-binding lectin, HLA-Bw4 and HLA-C) are involved in the innate immune system; and older, smaller studies have reported similar associations [100][101][102]. Further studies are needed to determine the mechanisms by which these polymorphisms are associated with a lack of EBV infection, and whether other genes are similarly associated with EBV serostatus.…”

Section: Viewpoints Papersmentioning

confidence: 99%

Predictors of Epstein-Barr virus serostatus and implications for vaccine policy: A systematic review of the literature

Winter

Jackson

Lewis

et al. 2020

Journal of Global Health

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Background Epstein-Barr virus (EBV) is an important human pathogen; it infects >90% people globally and is linked to infectious mononucleosis and several types of cancer. Vaccines against EBV are in development. In this study we present the first systematic review of the literature on risk factors for EBV infection, and discuss how they differ between settings, in order to improve our understanding of EBV epidemiology and aid the design of effective vaccination strategies.Methods MEDLINE, Embase, and Web of Science were searched on 6 th March 2017 for observational studies of risk factors for EBV infection. Studies were excluded if they were published before 2008 to ensure relevance to the modern day, given the importance of influencing future vaccination policies. There were no language restrictions. After title, abstract and full text screening, followed by checking the reference lists of included studies to identify further studies, data were extracted into standardised spreadsheets and quality assessed. A narrative synthesis was undertaken.Results Seventy-seven papers met our inclusion criteria, including data from 31 countries. There was consistent evidence that EBV seroprevalence was associated with age, increasing throughout childhood and adolescence and remaining constant thereafter. EBV was generally acquired at younger ages in Asia than Europe/North America. There was also compelling evidence for an association between cytomegalovirus infection and EBV. Additional factors associated with EBV seroprevalence, albeit with less consistent evidence, included ethnicity, socioeconomic status, other chronic viral infections, and genetic variants of HLA and immune response genes. ConclusionsOur study is the first systematic review to draw together the global literature on the risk factors for EBV infection and includes an evaluation of the quality of the published evidence. Across the literature, the factors examined are diverse. In Asia, early vaccination of infants would be required to prevent EBV infection. In contrast, in Western countries a vaccine could be deployed later, particularly if it has only a short duration of protection and the intention was to protect against infectious mononucleosis. There is a lack of high-quality data on the prevalence and age of EBV infection outside of Europe, North America and South-East Asia, which are essential for informing effective vaccination policies in these settings.

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“…The three different HLA-II molecules are HLA-DP, -DQ, and -DR ( 28 ). Each of these genotypes plays a critical role in EBV infection ( 29 ). In 2000, Haan et al found the transient expression of HLA-DQ rendered EBV entry, and further research showed that only the HLA-DQβ*02 locus could regulate EBV entry ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

“…In 2002, Mullen et al showed that the gp42 protein of EBV interacted with HLA-DR1 at a resolution of 2.65 Å ( 13 ). Li et al found that EBV infection of B cells could be impaired by blocking the interaction between gp42 and HLA-II molecules or blocking the conversion of gp42 into sgp42 ( 29 ). There is a hypothesis that the conformation of gp42 changes slightly after HLA-II molecules bind to gp42, which rearranges the relevant glycoproteins in the viral envelope and alters the infection process, suggesting that gp42 plays a key role during EBV infection ( 31 ).…”

Section: Discussionmentioning

confidence: 99%