Epstein-Barr Virus Genotypes and Strains in Central Nervous System Demyelinating Disease and Epstein-Barr Virus-Related Illnesses in Australia

Abstract

Objectives: To identify Epstein-Barr virus (EBV) genotypes and strains in samples from individuals with and without a first diagnosis of central nervous system (CNS) demyelinating disease (a possible precursor to multiple sclerosis) and patients with EBV-associated diseases in Australia. Methods: Samples from 55 EBV DNA and serology positive subjects including individuals with (n = 17) and without (n = 21) a first clinical diagnosis of CNS demyelination and patients with EBV-related diseases (n = 17) were examined. EBV genotype and strain were identified by sequence mutations within the Epstein-Barr nuclear antigen-2 region (EBNA-2) using DNA sequence analysis. Results: Both EBV genotypes, A and B, were detected (genotype A, 54/55, 98.2%; genotype B, 1/55, 1.8%). Within genotype A, GD1 was the most commonly detected strain (42/54, 77.7%), followed by B95-8 (9/54, 16.7%) and M-ABA (3/54, 5.6%). Genotype B, strain AG876, was found in one individual with CNS demyelinating disease. Conclusions: EBV genotype A and the GD1 strain were the common EBV genotypes isolated from individuals with and without CNS demyelinating disease, and in subjects with various EBV-related diseases. Although disease-specific genotypes or strains were not identified, this study provides useful insights into the molecular epidemiology of EBV infection in Australia.

Significance of Epstein-Barr virus (HHV-4) and CMV (HHV-5) infection among subtype-C human immunodeficiency virus-infected individuals

“…The 15 individuals who presented with cryptococcosis in this study, 12 were on antifungal drugs like liposomal amphotericin B study also reported non-association of EBV genotypes with EBV-associated disease. [28] In contrast we observed a higher percentage (70%) of EBV-2 genotype compared to EBV-1 in our study populations. In our previous study, we reported EBV and CMV genotypes from HIV-1-infected individuals with CNS-related opportunistic infections.…”

Epstein-Barr virus genetic variants are associated with multiple sclerosis

“…In all cases, the consensus sequence deriving from deep sequencing coincided with the one determined by Sanger sequencing, confirming the cosegregation of newly identified variants with the known EBNA2 alleles. We also found one or more variable positions in all HDs (1-17) and individuals with MS (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). For all couples of variants lying on the same read (coverage $50), the hypothesis of independent segregation, indicative of random sequencing errors, was rejected through a x 2 test (p , 0.05), thus supporting the coexistence of different genotypes.…”

“…Moreover, patients are more likely to harbor newly identified 1.2 allele-related variants, particularly at amino acid position 245. Previous studies on a possible association between EBV genotypes and MS generated mixed results, including the following: no association with EBNA6, EBNA1, and latent membrane protein, or EBNA2 [9][10][11][12] ; "marginally different frequencies" for tegument protein BRRF2 and EBNA1…”

“…7 To disclose possible MS-related EBV strains, various groups have followed a candidate-gene approach. [8][9][10][11][12][13][14] Along the same line, we chose to investigate EBV variability in MS by studying Epstein-Barr nuclear antigen 2 (EBNA2). EBNA2 is, in principle, the best candidate for this kind of study because it is the most polymorphic among all EBV genes: 5 major alleles of the EBV type 1 strain, the most frequent strain in the general Caucasian population, 15 have been identified based on nucleotide variations within the most variable region of EBNA2, which is also involved in the interaction with host proteins.…”

Epstein–Barr Virus Strain Variation

“…Type 1 is the main EBV prevalent worldwide, but in sub-Saharan Africa, type 2 EBV is equally abundant and there are many mixed infections. In Argentina, type 1 was present in 76 % of healthy carriers, type 2 in 15 %, and co-infections with both types in 7 % (Correa et al 2004); in Mexico, 33 % had type 1, 57 % had type 2 and 10 % had mixed infection (Palma et al 2013), but in Australia, 98 % of infections were type 1 (Lay et al 2012). Sequencing of type 2 EBV from the AG876 cell line enabled a comparison between type 1 and type 2 EBV genomes (Dolan et al 2006).…”