SEROPREVALENCE AND PHYLOGENETIC GENOTYPING OF EPSTEIN BARR VIRUS (EBV) AMONG BLOOD DONORS IN QATAR

Background: EBV is a lymphotropic herpesvirus and the causative agent of infectious mononucleosis. EBV is highly prevalent and has been linked to several malignancies. The virus is generally transferred by oral secretions and it persists as a latent infection in human B-cells. However, it can be also transmitted through blood transfusions and organ transplantations. The goal of this study was to (i) estimate the rate of infection of EBV in Qatar in healthy individuals, using serological testing, and viral load quantification, to (ii) study the correlation of EBV with demographic markers, and to (iii) study the molecular similarity of EBV isolates, using phylogenetic genotyping. Materials and methods: For estimating EBV seroprevalence, qualitative ELISA kits for detecting the following EBV antibodies were used: EBV viral capsid antigen (VCA) IgG & IgM, EBV nuclear antigen (EBNA) IgG & IgM, and early antigen (EA-D) IgG. To study the EBV viremia rate, DNA extracted from the buffy coat was subjected for viral detection and quantification using RT-PCR. For genotyping, nested PCR targeting the EBNA2 gene was used. And for further sub genotyping, the highly variable LMP-1 gene was amplified, cloned, sequenced and used for phylogenetic analysis. Results: Out of 673 analyzed samples (223 Qataris, 450 non-Qatari residents), 659 (97.9%) were EBV seropositive with different infection stages. Interestingly, 14 (2.1%) tested negative for all anti-EBV antibodies indicating no prior exposure to EBV. EBV DNA was detected in 354/673 (52.6%). Both EBV seroprevalence and viremia rate increased significantly with age. Genotyping for 51 randomly selected positive DNA samples showed that Genotype 1 was predominating, found in 36/51 (72.5%), while genotype 2 was found in 12 (23.5%) samples. Mixed infection was found in 2 (3.9%) samples. Surprisingly, Sub genotyping for 30 samples revealed that all tested clones (n=119) have the South Eastern Asia 1 (SEA1) strain. 30-bp and 69 bp deletions in the LMP-1 were also found in 10% and 13.3% samples, respectively. Conclusion: This is the first study investigating the seroprevalence, the viremia rate, and the molecular epidemiology of EBV among blood donors in Qatar. Hence, it should provide the epidemiologists, blood banks’ personnel, researchers and clinicians with EBV prevalence estimates and molecular epidemiology of EBV as a highly prevalent transfusion transmissible oncovirus

Epidemiological, Molecular, and Clinical Features of Norovirus Infections among Pediatric Patients in Qatar

Abstract: Background: Norovirus (NoV) is recognized as the second most important etiological agent leading to acute gastroenteritis globally. In order to determine the burden and characteristics of NoV infections in children in Qatar, profiling of circulating genotypes and their correlation with demographics and clinical manifestations were evaluated. Methods: A total of 177 NoV-positive fecal samples were collected from children suffering from acute gastroenteritis (AGE) during two-year period between June 2016 and June 2018. The age of the subjects ranged between 3 months and 12 years (median of 15 months). Genotyping was performed by amplifying and sequencing parts of viral VP1 and RNA-dependent RNA polymerase (RdRp) regions. Phylogenetic analysis and evolutionary relationships were performed using MEGA7.0. Fisher’s exact test was used to run statistical analysis for the clinical and demographical characteristics of circulating strains. Results: Overall, NoV infections were relatively higher in males than females with a ratio of 1.3:1 (p = 0.0073). Most of the NoV infections were reported in children between 1 and 3 years old (49.7%), followed by those 3 years of age (41.2% and 9.1%, respectively). NoV infections occurred throughout the year, with a noticeable increase in summer (36.6%) and drop in winter (25.4%). Nearly all (98.8%) NoV-infected children were positive for genogroup II (GII) compared to only two samples (1.2%) being positive for genogroup I (GI): GI.3 and GI.4. NoV genotype GII.4 (62.2%), GII.2 (15.8%), and GII.3 (13.5%) were predominant in our study. The detected strains shared >98% sequence homology with emerging recombinant strain of GII.P16-GII.4/RUS/Novosibirsk/2017 (MG892929), GII.P16-GII.4 Sydney/2012 (KY887601), GII.4 Sydney/2012, recombinant GII.P4 New Orleans /2009/GII.4 Sydney 2012 (MG585810.1), and the emerging strain GII.P16-GII.2 CHN/2017 (MH321823). Severe clinical illness (vesikari score >10) was reported in children infected with genotypes sharing homology with the above emerging strains. While GII.4 was reported in all age groups, NoV GII.3 infections were higher in children <1 year of age. Both genogroups (GII.4 and GII.3) in addition to GII.2 reported higher incidence in Qatari subjects compared to other nationalities (p = 0.034). Conclusion: This is the first report about NoV molecular epidemiology in Qatar. The most detected NoV strain was genogroup GII, which is the dominant genotype in the Middle East region. Further, we report GII.4, GII.2, and GII.3 as the most predominant NoV genotypes in our study. Moreover, disease severity scores were higher among children genotyped with genogroup GI (GI.4) and genogroup GII (GII.4, GII.2, GII.3, GII.6, and GII.7)

Viral-Induced Enhanced Disease Illness

Understanding immune responses to viral infections is crucial to progress in the quest for effective infection prevention and control. The host immunity involves various mechanisms to combat viral infections. Under certain circumstances, a viral infection or vaccination may result in a subverted immune system, which may lead to an exacerbated illness. Clinical evidence of enhanced illness by preexisting antibodies from vaccination, infection or maternal passive immunity is available for several viruses and is presumptively proposed for other viruses. Multiple mechanisms have been proposed to explain this phenomenon. It has been confirmed that certain infection- and/or vaccine-induced immunity could exacerbate viral infectivity in Fc receptor- or complement bearing cells- mediated mechanisms. Considering that antibody dependent enhancement (ADE) is a major obstacle in vaccine development, there are continues efforts to understand the underlying mechanisms through identification of the epitopes and antibodies responsible for disease enhancement or protection. This review discusses the recent findings on virally induced ADE, and highlights the potential mechanisms leading to this condition

Viruses and Autoimmunity: A Review on the Potential Interaction and Molecular Mechanisms.

For a long time, viruses have been shown to modify the clinical picture of several autoimmune diseases, including type 1 diabetes (T1D), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome (SS), herpetic stromal keratitis (HSK), celiac disease (CD), and multiple sclerosis (MS). Best examples of viral infections that have been proposed to modulate the induction and development of autoimmune diseases are the infections with enteric viruses such as Coxsackie B virus (CVB) and rotavirus, as well as influenza A viruses (IAV), and herpesviruses. Other viruses that have been studied in this context include, measles, mumps, and rubella. Epidemiological studies in humans and experimental studies in animal have shown that viral infections can induce or protect from autoimmunopathologies depending on several factors including genetic background, host-elicited immune responses, type of virus strain, viral load, and the onset time of infection. Still, data delineating the clear mechanistic interaction between the virus and the immune system to induce autoreactivity are scarce. Available data indicate that viral-induced autoimmunity can be activated through multiple mechanisms including molecular mimicry, epitope spreading, bystander activation, and immortalization of infected B cells. Contrarily, the protective effects can be achieved via regulatory immune responses which lead to the suppression of autoimmune phenomena. Therefore, a better understanding of the immune-related molecular processes in virus-induced autoimmunity is warranted. Here we provide an overview of the current understanding of viral-induced autoimmunity and the mechanisms that are associated with this phenomenon

Prevalence and molecular profiling of Epstein Barr virus (EBV) among healthy blood donors from different nationalities in Qatar

Background The Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis. EBV is highly prevalent lymphotropic herpesvirus and has been linked to several malignancies. Transmission is generally by oral secretions, but can be through blood transfusions and organ transplantations. This study aimed to determine the seroprevalence, viremia rates, and circulating genotypes of EBV in healthy blood donors in Qatar. Methods Blood samples from 673 blood donors of different nationalities residing in Qatar (mainly Qatar, Egypt, Syria, Jordan, Pakistan, and India) were collected and tested for anti-EBV capsid (VCA; IgG & IgM), nuclear (EBNA; IgG), and early (EA-D; IgG) antigens. Avidity testing was determined when active infection was suspected. DNA was extracted from the buffy coat and subjected to EBV-DNA quantification using qRT-PCR. Genotyping was performed using nested-PCR targeting EBV-EBNA2 gene, and phylogeny by sequence analysis of the LMP-1 gene. Results 97.9% (673/659) of the samples were seropositive as indicated by the presence VCA-IgG, while 52.6% (354/673) had detectible EBV-DNA. EBV seroprevalence and viremia rates increased significantly with age. Genotyping of 51 randomly selected samples showed predominance of Genotype 1 (72.5%, 37/51) as compared to genotype 2 (3.5%), and mixed infections were detected in 4% of the samples. Sub-genotyping for these samples revealed that the Mediterranean strain was predominant (65.3%), followed by B95.8 prototype and North Carolina strains (12.2% each), and China1 strain (6%). Conclusion As a first study to evaluate EBV infection in highly diverse population in Qatar, where expatriates represent more than 85% of the population, our results indicated high seroprevalence and viremia rate of EBV in different nationalities, with genotype 1 and Mediterranean strain being predominant. Clinical significance of these finding have not been investigated and shall be evaluated in future studies. 1 2017 Smatti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This work was made possible by UREP grant # (UREP18-001-3-001) from the Qatar National Research Fund (a member of Qatar Foundation). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We are grateful to: Ms. Enas Al Absi, Mr. Mohamed El Zowalaty and Mrs. Nadima Ali, and the following students: Mariam Nofal, Rana Al Disi and Soumaya Harche for their technical support. This work was made possible by UREP grant # (UREP18-001-3-001) from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the author(s). This sample collection was approved by the Hamad Medical Center Research Committee (Protocol #13422/13).Scopu

Genome-wide association study identifies several loci for HEV seropositivity

Hepatitis E viral (HEV) infection imposes a heavy global health burden. The variability in the prevalence of serological markers of HEV infection between different ethnic groups proposes a host genetic influence. Here, we report genetic polymorphisms associated with anti-HEV antibody positivity and level using binary- and quantitative-trait genome-wide association studies (GWAS) on a population from Qatar (n = 5829). We identified a region in 12p11.1 (lead SNP: rs559856097, allele: A, p = 2.3 × 10−10) significantly associated with anti-HEV antibodies level. This intergenic variant is located near SNORD112, a small nucleolar RNA (snoRNA). Additional gene-set and pathway enrichment analyses highlighted a strong correlation with anti-viral response-related pathways, including IFNs (alpha/beta) and interleukin-21 (IL-21) signaling. This is the first GWAS on the response to HEV infection. Further replication and functional experimentation are warranted to validate these findings.This study was funded by Qatar University High Impact Grant (Grant number: QUHI-BRC-20_21-1). The work makes use of data generated by the Qatar Genome Program (QGP) and Qatar Biobank (QBB), which are funded by Qatar foundation for Education, Science and Community

Host Genetic Variants Potentially Associated With SARS-CoV-2: A Multi-Population Analysis.

Clinical outcomes of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) showed enormous inter-individual and inter-population differences, possibly due to host genetics differences. Earlier studies identified single nucleotide polymorphisms (SNPs) associated with SARS-CoV-1 in Eastern Asian (EAS) populations. In this report, we aimed at exploring the frequency of a set of genetic polymorphisms that could affect SARS-CoV-2 susceptibility or severity, including those that were previously associated with SARS-CoV-1. We extracted the list of SNPs that could potentially modulate SARS-CoV-2 from the genome wide association studies (GWAS) on SARS-CoV-1 and other viruses. We also collected the expression data of these SNPs from the expression quantitative trait loci (eQTLs) databases. Sequences from Qatar Genome Programme (QGP, = 6,054) and 1000Genome project were used to calculate and compare allelic frequencies (AF). A total of 74 SNPs, located in 10 genes: , -γ, , , , , , , and promoter, were identified. Analysis of Qatari genomes revealed significantly lower AF of risk variants linked to SARS-CoV-1 severity (, , , , and ) compared to that of 1000Genome and/or the EAS population (up to 25-fold change). Conversely, SNPs in , -γ, , and were more common among Qataris (average 2-fold change). Inter-population analysis showed that the distribution of risk alleles among Europeans differs substantially from Africans and EASs. Remarkably, Africans seem to carry extremely lower frequencies of SARS-CoV-1 susceptibility alleles, reaching to 32-fold decrease compared to other populations. Multiple genetic variants, which could potentially modulate SARS-CoV-2 infection, are significantly variable between populations, with the lowest frequency observed among Africans. Our results highlight the importance of exploring population genetics to understand and predict COVID-19 outcomes. Indeed, further studies are needed to validate these findings as well as to identify new genetic determinants linked to SARS-CoV-2.This work was supported by the Qatar University High Impact Grant (Grant Number: QUHI-BRC-20_21-1). OA was supported by a startup grant from the College of Health and Life Sciences, Hamad Bin Khalifa University. This work makes use of data generated by the Qatar Genome Programme (QGP) and Qatar Biobank (QBB), which are funded by Qatar Foundation for Education, Science and Community

Will Host Genetics Affect the Response to SARS-CoV-2 Vaccines? Historical Precedents

Recent progress in genomics and bioinformatics technologies have allowed for the emergence of immunogenomics field. This intersection of immunology and genetics has broadened our understanding of how the immune system responds to infection and vaccination. While the immunogenetic basis of the huge clinical variability in response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently being extensively studied, the host genetic determinants of SARS-CoV-2 vaccines remain largely unknown. Previous reports evidenced that vaccines may not protect all populations or individuals equally, due to multiple host- and vaccine-specific factors. Several studies on vaccine response to measles, rubella, hepatitis B, smallpox, and influenza highlighted the contribution of genetic mutations or polymorphisms in modulating the innate and adaptive immunity following vaccination. Specifically, genetic variants in genes encoding virus receptors, antigen presentation, cytokine production, or related to immune cells activation and differentiation could influence how an individual responds to vaccination. Although such knowledge could be utilized to generate personalized vaccine strategies to optimize the vaccine response, studies in this filed are still scarce. Here, we briefly summarize the scientific literature related to the immunogenetic determinants of vaccine-induced immunity, highlighting the possible role of host genetics in response to SARS-CoV-2 vaccines as well.This work was supported by the Qatar University High Impact Grant (Grant Number: QUHI-BRC-20_21-1) and Student Grant (Grant Number: QUST-1-BRC-2022-399)