Coevolution of Sites under Immune Selection Shapes Epstein–Barr Virus Population Structure

Abstract Epstein–Barr virus (EBV) is one of the most common viral infections in humans and persists within its host for life. EBV therefore represents an extremely successful virus that has evolved complex strategies to evade the host’s innate and adaptive immune response during both initial and persistent stages of infection. Here, we conducted a comparative genomics analysis on 223 whole genome sequences of worldwide EBV strains. We recover extensive genome-wide linkage disequilibrium (LD) despite pervasive genetic recombination. This pattern is explained by the global EBV population being subdivided into three main subpopulations, one primarily found in East Asia, one in Southeast Asia and Oceania, and the third including most of the other globally distributed genomes we analyzed. Additionally, sites in LD were overrepresented in immunogenic genes. Taken together, our results suggest that host immune selection and local adaptation to different human host populations has shaped the genome-wide patterns of genetic diversity in EBV.

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

Genome Biology and Evolution ◽

10.1093/gbe/evu054 ◽

2014 ◽

Vol 6 (4) ◽

pp. 846-860 ◽

Cited By ~ 44

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

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Fidelity of SNP Array Genotyping Using Epstein Barr Virus-Transformed B-Lymphocyte Cell Lines: Implications for Genome-Wide Association Studies

PLoS ONE ◽

10.1371/journal.pone.0006915 ◽

2009 ◽

Vol 4 (9) ◽

pp. e6915 ◽

Cited By ~ 25

Author(s):

Joshua T. Herbeck ◽

Geoffrey S. Gottlieb ◽

Kim Wong ◽

Roger Detels ◽

John P. Phair ◽

...

Keyword(s):

Epstein Barr Virus ◽

B Lymphocyte ◽

Association Studies ◽

Snp Array ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Barr Virus ◽

Genome Wide ◽

Epstein Barr ◽

Lymphocyte Cell

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Acute Pharyngitis: Etiology and Diagnosis

PEDIATRICS ◽

10.1542/peds.97.6.949 ◽

1996 ◽

Vol 97 (6) ◽

pp. 949-954

Author(s):

Alan L. Bisno

Keyword(s):

Herpes Simplex ◽

Influenza A ◽

Epstein Barr Virus ◽

Viral Infections ◽

Clinical Manifestations ◽

Acute Pharyngitis ◽

Herpesvirus Type ◽

Barr Virus ◽

Epstein Barr

Acute pharyngitis may be caused by a wide variety of microbial agents (Table 1). The relative importance of each of these agents varies greatly depending on a number of epidemiologic factors, including age of the patient, season of the year, and geographic locale. Viruses Most cases of acute pharyngitis are viral in etiology and involve the pharynx as well as other portions of the respiratory tract as manifestations of the common cold, influenza, or croup. Examples include the rhinoviruses, coronaviruses, influenza A and B, and the parainfluenza viruses. Certain viral infections causing sore throat may exhibit clinical manifestations that are rather distinctive. Examples include enteroviruses (herpangina due to Coxsackie A), Epstein-Barr virus (infectious mononucleosis), cytomegalovirus (cytomegalovirus mononucleosis), adenovirus (pharyngoconjunctival fever, acute respiratory disease of military recruits), and herpes simplex virus (pharyngitis, gingivitis, and stomatitis). In many instances, however, the illnesses caused by these agents may overlap so broadly with that of streptococcal pharyngitis as to be clinically indistinguishable. Thus, Epstein-Barr virus, adenovirus, and herpes virus may all cause fever, exudative pharyngitis, and cervical adenitis. Several studies have documented the role of primary herpesvirus type 1 infection as a cause of acute pharyngitis in college students.1-4 Herpesvirus type 2 can occasionally cause a similar illness as a consequence of oral-genital sexual contact.5 Although herpesvirus infections may involve the anterior oral cavity (vesicular or ulcerative gingivostomatitis) as well as the posterior pharynx, they do not routinely do so. Only about one-fourth of students with culturally and serologically proven primary herpes simplex type 1 pharyngitis studied by Glezen et al,2 for example, had gingivostomatitis.

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Pancytopenia Secondary to SARS-CoV 2 Infection-A Case Reprt

10.21203/rs.3.rs-657352/v1 ◽

2021 ◽

Author(s):

Neeraj Sharma ◽

Rajat Shukla ◽

Rachna Warrier ◽

Kunal Kumar ◽

Nalin Singh ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Blood Cells ◽

Epstein Barr Virus ◽

Viral Infections ◽

Parvovirus B19 ◽

Rare Complication ◽

Elderly Male ◽

Barr Virus ◽

Immunodeficiency Virus ◽

Epstein Barr

Abstract Pancytopenia is a condition when person has low count of all three types of blood cells causing a triage of anemia, leukopenia and thrombocytopenia. It should not be considered as a disease in itself but rather the sign of a disease that needs to be further evaluated. Among the various causes, viral infections like Human Immunodeficiency Virus, Cytomegalovirus, Epstein-Barr virus and Parvovirus B19 have been implicated. Pancytopenia is a rare complication and not commonly seen in patients with COVID 19 disease. Here, we report a case of pancytopenia in previously immunocompetent elderly male patient with SARS-CoV2 infection.

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

10.1101/689216 ◽

2019 ◽

Cited By ~ 1

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.

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Profound CD4+ T lymphocytopenia in human immunodeficiency virus negative individuals, improved with anti-human herpes virus treatment

Colombia Medica ◽

10.25100/cm.v43i4.1159 ◽

2012 ◽

pp. 305-311 ◽

Cited By ~ 3

Author(s):

María Lilia Diaz Betancourth ◽

Julio Cesar Klinger ◽

Victoria Eugenia Niño

Keyword(s):

Human Immunodeficiency Virus ◽

Epstein Barr Virus ◽

Herpes Virus ◽

Viral Infections ◽

Human Herpes ◽

Barr Virus ◽

Human Herpes Virus ◽

Immunodeficiency Virus ◽

Epstein Barr ◽

Herpès Virus

Lymphocytopenia and CD4+ T lymphocytopenia can be associated with many bacterial, fungal, parasite and viral infections. They can also be found in autoimmune and neoplastic diseases, common variable immunodeficiency syndrome, physical, psychological and traumatic stress, malnutrition and immunosuppressive therapy. Besides, they can also be brought into relation, without a known cause, with idiopathic CD4+ T lymphocytopenia. Among viral infections, the Retrovirus, specially the human immunodeficiency virus, is the most frequently cause. However, many acute viral infections, including cytomegalovirus and Epstein Barr virus can be associated with transient lymphocytopenia and CD4+ T lymphocytopenia. As is well known, transient lymphocytopenia and CD4+ T lymphocytopenia are temporary and overcome when the disease improves. Nonetheless, severe CD4+ T Lymphocytopenia associated with chronic infections by human herpes virus has not been reported. We describe 6 cases of human immunodeficiency virus negative patients, with chronic cytomegalovirus and Epstein Barr virus infections and profound lymphocytopenia with clinical symptoms of cellular immunodeficiency. These patients improved rapidly with ganciclovir or valganciclovir treatment. We claim here that it is important to consider the chronic human herpes virus infection in the differential diagnosis of profoundly CD4+ T lymphocytopenia etiology, when human immunodeficiency virus is absent, in order to start effective treatment and to determine, in future studies, the impact of chronic human herpes virus infection in human beings’ health.

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Determination and genome-wide analysis of Epstein-Barr virus (EBV) sequences in EBV-associated gastric carcinoma from Guangdong, an endemic area of nasopharyngeal carcinoma

Journal of Medical Microbiology ◽

10.1099/jmm.0.000839 ◽

2018 ◽

Vol 67 (11) ◽

pp. 1614-1627 ◽

Cited By ~ 3

Author(s):

Jian-ning Chen ◽

Lu Zhou ◽

Xin-min Qiu ◽

Ri-hong Yang ◽

Jing Liang ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Gastric Carcinoma ◽

Endemic Area ◽

Epstein Barr Virus ◽

Genome Wide Analysis ◽

Barr Virus ◽

Genome Wide ◽

Epstein Barr

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Other Viral Infections Epstein Barr Virus, Cytomegalovirus, Parvovirus, Hantavirus, Marburg/Ebola Virus, Chandipura Virus

Textbook of Medicine ◽

10.5005/jp/books/10921_61 ◽

2008 ◽

pp. 347-347

Author(s):

K.V. Das

Keyword(s):

Epstein Barr Virus ◽

Ebola Virus ◽

Viral Infections ◽

Barr Virus ◽

Chandipura Virus ◽

Epstein Barr

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

Multiple Sclerosis Journal ◽

10.1177/1352458515626598 ◽

2016 ◽

Vol 22 (13) ◽

pp. 1655-1664 ◽

Cited By ~ 25

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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