Abstract
BackgroundDiseases associated with Epstein-Barr virus (EBV) infections, such as infectious mononucleosis (IM), EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) and chronic active EBV infection (CAEBV) are not rare in Chinese children. The association of type 1 or type 2 EBV and variants of the EBV BZLF1 promoter zone (Zp) with these diseases is unclear.ResultsThe objective of this study was to investigate the relationship between EBV genotypes (Zp variants and EBV type 1 and 2) and the clinical phenotypes of EBV-associated diseases in Chinese children. The Zp region was directly sequenced in 206 EBV-positive DNA samples from the blood of patients with IM, EBV-HLH, CAEBV, and healthy controls. Type 1 or type 2 EBV was examined by PCR for EBNA2 and EBNA3C subtypes. Four polymorphic Zp variants were identified: Zp-P, Zp-V3, Zp-P4 and Zp-V1, a new variant. The Zp-V3 variant was significantly associated with CAEBV (P ≤ 0.01). The frequency of co-infection with Zp variants was higher in patients with CAEBV and EBV-HLH, compared with IM and healthy controls, mostly as Zp-P+V3 co-infection. Type 1 EBV was predominant in all categories (81.3-95%) and there was no significant difference in the frequency of the EBV types 1 and 2 in different categories (P > 0.05).ConclusionsType 1 EBV and BZLF1 Zp-P of EBV were the predominant genotypes in nonmalignant EBV associated diseases in Chinese children and Zp-V3 variant may correlates with the developing of severe EBV infection diseases, such as CAEBV and EBV-HLH.
Highlights
Diseases associated with Epstein-Barr virus (EBV) infections, such as infectious mononucleosis (IM), EBVassociated hemophagocytic lymphohistiocytosis (EBV-HLH) and chronic active EBV infection (CAEBV) are not rare in Chinese children
Zp variants in EBV infected children Sequence differences identified within the major regulatory Zp domains of EBV infected individuals can be grouped into four variant forms (Figure 1)
We found that Zp-P variant was the dominant genotype found in all infection categories, except a relatively rare diseaseCAEBV, indicating that it was the primary variant of EBV circulating in China
Summary
Diseases associated with Epstein-Barr virus (EBV) infections, such as infectious mononucleosis (IM), EBVassociated hemophagocytic lymphohistiocytosis (EBV-HLH) and chronic active EBV infection (CAEBV) are not rare in Chinese children. Epstein-Barr virus (EBV) is a member of the Lymphocryptovirus genus, Gammaherpesvirinae subfamily of the Herpesviridae family of viruses This virus is associated with a wide variety of diseases, both benign and malignant, which ubiquitously infect humans and persist for the lifetime of the individual. EBV genotypes can be categorized as type 1 or type 2 on the basis of marked allelic polymorphisms within the EBNA2, 3A, 3B, and 3C genes [3,4]. Both EBV types have been detected in immunocompromised and immunocompetent hosts but type 1 EBV is predominant in Asian nasopharyngeal carcinoma and has a greater potential to transform B lymphocytes than EBV type 2.
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