scholarly journals Genetic Analyses of Common Infections in the Avon Longitudinal Study of Parents and Children Cohort

2021 ◽  
Vol 12 ◽  
Author(s):  
Amanda H. W. Chong ◽  
Ruth E. Mitchell ◽  
Gibran Hemani ◽  
George Davey Smith ◽  
Robert H. Yolken ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Measles Virus ◽  
Hla Alleles ◽  
Barr Virus ◽  
Parents And Children ◽  
Genome Wide ◽  
Casein Protein ◽  
Epstein Barr ◽  
Antibody Levels ◽  
Virus Subtype

The burden of infections on an individual and public health is profound. Many observational studies have shown a link between infections and the pathogenesis of disease; however a greater understanding of the role of host genetics is essential. Children from the longitudinal birth cohort, the Avon Longitudinal Study of Parents and Children, had 14 antibodies measured in plasma at age 7: Alpha-casein protein, beta-casein protein, cytomegalovirus, Epstein-Barr virus, feline herpes virus, Helicobacter pylori, herpes simplex virus 1, influenza virus subtype H1N1, influenza virus subtype H3N2, measles virus, Saccharomyces cerevisiae, Theiler’s virus, Toxoplasma gondii, and SAG1 protein domain, a surface antigen of Toxoplasma gondii measured for greater precision. We performed genome-wide association analyses of antibody levels against these 14 infections (N = 357 – 5010) and identified three genome-wide signals (P < 5×10-8), two associated with measles virus antibodies and one with Toxoplasma gondii antibodies. In an association analysis focused on the human leukocyte antigen (HLA) region of the genome, we further detected 15 HLA alleles at a two-digit resolution and 23 HLA alleles at a four-digit resolution associated with five antibodies, with eight HLA alleles associated with Epstein-Barr virus antibodies showing strong evidence of replication in UK Biobank. We discuss how our findings from antibody levels complement other studies using self-reported phenotypes in understanding the architecture of host genetics related to infections.

scholarly journals Genetic analyses of common infections in the Avon Longitudinal Study of Parents and Children cohort

2021 ◽  
Author(s):  
Amanda HW Chong ◽  
Ruth E Mitchell ◽  
Gibran Hemani ◽  
George Davey Smith ◽  
Rebecca C Richmond ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Measles Virus ◽  
Hla Alleles ◽  
Barr Virus ◽  
Parents And Children ◽  
Genome Wide ◽  
Casein Protein ◽  
Epstein Barr ◽  
Avon Longitudinal Study ◽  
Virus Subtype

The burden of infections on an individual and public health is profound. Many observational studies have shown a link between infections and the pathogenesis of disease; however a greater understanding of the role of host genetics is essential. Children from the longitudinal birth cohort, the Avon Longitudinal Study of Parents and Children, had 14 antibodies measured in plasma at age 7: Alpha-casein protein, beta-casein protein, cytomegalovirus, Epstein-Barr virus, feline herpes virus, Helicobacter pylori, herpes simplex virus 1, influenza virus subtype H1N1, influenza virus subtype H3N2, measles virus, Saccharomyces cerevisiae, Theiler's virus, Toxoplasma gondii, and SAG1 protein domain, a surface antigen of Toxoplasma gondii measured for greater precision. We performed genome-wide association analyses of antibody levels against 14 infections (N = 357-5010) and identified three genome-wide signals (P < 5x10-8), two associated with measles virus antibodies and one with Toxoplasma gondii antibodies. In an association analysis focused on the human leukocyte antigen (HLA) region of the genome, we further detected 15 HLA alleles at a two-digit resolution and 23 HLA alleles at a four-digit resolution associated with five antibodies, with eight HLA alleles associated with Epstein-Barr virus antibodies showing strong evidence of replication in UK Biobank. Our findings provide a useful resource for any future studies using the ALSPAC infection data and contributes to the understanding of the architecture of host genetics related to infections.

scholarly journals Genome-Wide Analysis of Wild-Type Epstein–Barr Virus Genomes Derived from Healthy Individuals of the 1000 Genomes Project

2014 ◽  
Vol 6 (4) ◽  
pp. 846-860 ◽  
Author(s):  
Gabriel Santpere ◽  
Fleur Darre ◽  
Soledad Blanco ◽  
Antonio Alcami ◽  
Pablo Villoslada ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Healthy Individuals ◽  
Wild Type ◽  
1000 Genomes Project ◽  
Genome Wide Analysis ◽  
Barr Virus ◽  
1000 Genomes ◽  
Genome Wide ◽  
Epstein Barr ◽  
Virus Genomes

scholarly journals Epstein Barr virus genomes reveal population structure and type 1 association with endemic Burkitt lymphoma

2019 ◽  
Author(s):  
Yasin Kaymaz ◽  
Cliff I. Oduor ◽  
Ozkan Aydemir ◽  
Micah A. Luftig ◽  
Juliana A. Otieno ◽  
...  
Keyword(s):  
Population Structure ◽  
Burkitt Lymphoma ◽  
Epstein Barr Virus ◽  
Genome Wide Association ◽  
Viral Dna ◽  
Barr Virus ◽  
Genome Wide ◽  
Epstein Barr

AbstractEndemic Burkitt lymphoma (eBL), the most prevalent pediatric cancer in sub-Saharan Africa, is associated with malaria and Epstein Barr virus (EBV). In order to better understand the role of EBV in eBL, we improved viral DNA enrichment methods and generated a total of 98 new EBV genomes from both eBL cases (N=58) and healthy controls (N=40) residing in the same geographic region in Kenya. Comparing cases and controls, we found that EBV type 1 was significantly associated with eBL with 74.5% of patients (41/55) versus 47.5% of healthy children (19/40) carrying type 1 (OR=3.24, 95% CI=1.36 - 7.71,P=0.007). Controlling for EBV type, we also performed a genome-wide association study identifying 6 nonsynonymous variants in the genes EBNA1, EBNA2, BcLF1, and BARF1 that were enriched in eBL patients. Additionally, we observed that viruses isolated from plasma of eBL patients were identical to their tumor counterpart consistent with circulating viral DNA originating from the tumor. We also detected three intertypic recombinants carrying type 1 EBNA2 and type 2 EBNA3 regions as well as one novel genome with a 20 kb deletion resulting in the loss of multiple lytic and virion genes. Comparing EBV types, genes show differential variation rates as type 1 appears to be more divergent. Besides, type 2 demonstrates novel substructures. Overall, our findings address the complexities of EBV population structure and provide new insight into viral variation, which has the potential to influence eBL oncogenesis.Key PointsEBV type 1 is more prevalent in eBL patients compared to the geographically matched healthy control group.Genome-wide association analysis between cases and controls identifies 6 eBL-associated nonsynonymous variants in EBNA1, EBNA2, BcLF1, and BARF1 genes.Analysis of population structure reveals that EBV type 2 exists as two genomic sub groups.

Effect of high-dose vitamin D3 supplementation on antibody responses against Epstein–Barr virus in relapsing-remitting multiple sclerosis

2016 ◽  
Vol 23 (3) ◽  
pp. 395-402 ◽  
Author(s):  
Egil Røsjø ◽  
Andreas Lossius ◽  
Nada Abdelmagid ◽  
Jonas C Lindstrøm ◽  
Margitta T Kampman ◽  
...  
Keyword(s):  
Vitamin D ◽  
Epstein Barr Virus ◽  
High Dose ◽  
Oral Vitamin ◽  
Barr Virus ◽  
Relapsing Remitting ◽  
Dose Oral ◽  
Epstein Barr ◽  
Antibody Levels ◽  
Relapsing Remitting Multiple Sclerosis

Background: Elevated antibody levels against Epstein–Barr virus (EBV) and a poor vitamin D status are environmental factors that may interact in relapsing-remitting multiple sclerosis (RRMS) aetiology. Objectives: To examine effects of high-dose oral vitamin D3 supplementation on antibody levels against EBV nuclear antigen 1 (EBNA1) in RRMS. Methods: Serum 25-hydroxyvitamin D3 (25(OH)D) and immunoglobulin G antibody levels against EBNA1 (whole protein and amino acid 385–420 fragment), EBV viral capsid antigen (VCA), cytomegalovirus (CMV) and varicella zoster virus (VZV) were measured in 68 RRMS patients enrolled in a 96-week randomised double-blinded placebo-controlled clinical trial of oral vitamin D3 supplementation (20,000 IU/week) (NCT00785473). Results: The mean 25(OH)D level more than doubled in the vitamin D group and was significantly higher than in the placebo group at study conclusion (123.2 versus 61.8 nmol/L, p < 0.001). Compared to the placebo group, both anti-EBNA1 protein and fragment antibody levels decreased in the vitamin D group from baseline to week 48 ( p = 0.038 and p = 0.004, respectively), but not from baseline to week 96. Vitamin D3 supplementation did not affect antibodies against VCA, CMV or VZV. Conclusion: The results indicate that high-dose oral vitamin D3 supplementation can affect humoral immune responses against the latent EBV antigen EBNA1 in RRMS.

scholarly journals An overview of viral infections of the nervous system in the immunosuppressed

2020 ◽  
Author(s):  
Peter G. E. Kennedy
Keyword(s):  
Nervous System ◽  
Measles Virus ◽  
Viral Infections ◽  
Jc Virus ◽  
Virus Infections ◽  
Inborn Errors ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Epstein Barr ◽  
Simplex Virus

Abstract Several viruses have the capacity to cause serious infections of the nervous system in patients who are immunosuppressed. Individuals may be immunosuppressed because of primary inherited immunodeficiency, secondary immunodeficiency due to particular diseases such as malignancy, administration of immunosuppressant drugs or organ or bone marrow transplantation. The viruses capable of such opportunistic infection of the nervous system include herpes simplex virus (HSV), Varicella-Zoster virus (VZV), Cytomegalovirus (CMV), Epstein –Barr virus (EBV), Human Herpes virus type 6 (HHV-6), JC virus (JCV), enterovirus, measles virus and Covid-19. In most cases it seems likely that immunological defence mechanisms in the immunosuppressed are deficient which creates a suitable environment for certain viruses to become opportunistic in the nervous and other systems. Further research is required both to understand these opportunistic mechanisms in more detail and also to determine how many virus infections are modified by specific inborn errors of immunological responses.

scholarly journals Molecular mimicry between Anoctamin 2 and Epstein-Barr virus nuclear antigen 1 associates with multiple sclerosis risk

2019 ◽  
Vol 116 (34) ◽  
pp. 16955-16960 ◽  
Author(s):  
Katarina Tengvall ◽  
Jesse Huang ◽  
Cecilia Hellström ◽  
Patrick Kammer ◽  
Martin Biström ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
T Cell ◽  
Epstein Barr Virus ◽  
Molecular Mimicry ◽  
Nuclear Antigen ◽  
Immune Reactivity ◽  
Barr Virus ◽  
Epstein Barr ◽  
Antibody Levels

Multiple sclerosis (MS) is a chronic inflammatory, likely autoimmune disease of the central nervous system with a combination of genetic and environmental risk factors, among which Epstein-Barr virus (EBV) infection is a strong suspect. We have previously identified increased autoantibody levels toward the chloride-channel protein Anoctamin 2 (ANO2) in MS. Here, IgG antibody reactivity toward ANO2 and EBV nuclear antigen 1 (EBNA1) was measured using bead-based multiplex serology in plasma samples from 8,746 MS cases and 7,228 controls. We detected increased anti-ANO2 antibody levels in MS (P = 3.5 × 10−36) with 14.6% of cases and 7.8% of controls being ANO2 seropositive (odds ratio [OR] = 1.6; 95% confidence intervals [95%CI]: 1.5 to 1.8). The MS risk increase in ANO2-seropositive individuals was dramatic when also exposed to 3 known risk factors for MS: HLA-DRB1*15:01 carriage, absence of HLA-A*02:01, and high anti-EBNA1 antibody levels (OR = 24.9; 95%CI: 17.9 to 34.8). Reciprocal blocking experiments with ANO2 and EBNA1 peptides demonstrated antibody cross-reactivity, mapping to ANO2 [aa 140 to 149] and EBNA1 [aa 431 to 440]. HLA gene region was associated with anti-ANO2 antibody levels and HLA-DRB1*04:01 haplotype was negatively associated with ANO2 seropositivity (OR = 0.6; 95%CI: 0.5 to 0.7). Anti-ANO2 antibody levels were not increased in patients from 3 other inflammatory disease cohorts. The HLA influence and the fact that specific IgG production usually needs T cell help provides indirect evidence for a T cell ANO2 autoreactivity in MS. We propose a hypothesis where immune reactivity toward EBNA1 through molecular mimicry with ANO2 contributes to the etiopathogenesis of MS.

Genetic loci for Epstein-Barr virus nuclear antigen-1 are associated with risk of multiple sclerosis

2016 ◽  
Vol 22 (13) ◽  
pp. 1655-1664 ◽  
Author(s):  
Yuan Zhou ◽  
Gu Zhu ◽  
Jac C Charlesworth ◽  
Steve Simpson ◽  
Rohina Rubicz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Genetic Risk ◽  
Epstein Barr Virus ◽  
Meta Analysis ◽  
Nuclear Antigen ◽  
Genetic Loci ◽  
Polygenic Risk ◽  
Barr Virus ◽  
Genome Wide ◽  
Epstein Barr

Background: Infection with the Epstein-Barr virus (EBV) is associated with an increased risk of multiple sclerosis (MS). Objective: We sought genetic loci influencing EBV nuclear antigen-1 (EBNA-1) IgG titers and hypothesized that they may play a role in MS risk. Methods: We performed a genome-wide association study (GWAS) of anti-EBNA-1 IgG titers in 3599 individuals from an unselected twin family cohort, followed by a meta-analysis with data from an independent EBNA-1 GWAS. We then examined the shared polygenic risk between the EBNA-1 GWAS (effective sample size ( Neff) = 5555) and a large MS GWAS ( Neff = 15,231). Results: We identified one locus of strong association within the human leukocyte antigen (HLA) region, of which the most significantly associated genotyped single nucleotide polymorphism (SNP) was rs2516049 ( p = 4.11 × 10−9). A meta-analysis including data from another EBNA-1 GWAS in a cohort of Mexican-American families confirmed that rs2516049 remained the most significantly associated SNP ( p = 3.32 × 10−20). By examining the shared polygenic risk, we show that the genetic risk for elevated anti-EBNA-1 titers is positively correlated with the development of MS, and that elevated EBNA-1 titers are not an epiphenomena secondary to MS. In the joint meta-analysis of EBNA-1 titers and MS, loci at 1p22.1, 3p24.1, 3q13.33, and 10p15.1 reached genome-wide significance ( p < 5 × 10−8). Conclusions: Our results suggest that apart from the confirmed HLA region, the association of anti-EBNA-1 IgG titer with MS risk is also mediated through non-HLA genes, and that studies aimed at identifying genetic loci influencing EBNA immune response provides a novel opportunity to identify new and characterize existing genetic risk factors for MS.

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