Common Epstein-Barr virus (EBV) type-1 variant strains in both malignant and benign EBV-associated disorders.
In the present study, Epstein-Barr virus (EBV) isolates from 18 malignant tumors (angioimmunoblastic lymphadenopathy [AILD], n = 4; Hodgkin's disease [HD], n = 3; pleomorphic T-cell non-Hodgkin's lymphoma [T-NHL], n = 1; B-cell non-Hodgkin's lymphoma [B-NHL], n = 8; gastric carcinoma, n = 2) as well as from 10 tonsils of EBV-seropositive children and from peripheral blood mononuclear cells of 12 children with uncomplicated infectious mononucleosis (IM) and of a boy with severe chronic active EBV infection were genotyped in the EBV nuclear antigen-2 (EBNA-2) gene. A total of 40 of 41 isolates harbored EBV type 1; in 1 specimen (tonsil), only EBV type 2 was found. Further molecular characterization of EBV type-1 wild-type isolates in the EBNA-2 gene and in the 40-kb distant EBV-encoded small RNAs (EBER) region showed that different groups of stable EBV type-1 variant strains exist in vivo both in benign and malignant lymphatic tissue. Group 1 is composed of EBV type-1 isolates (B-NHL, n = 3; T-NHL, n = 1; HD, n = 1; IM, n = 4) that showed a B95-8-like DNA sequence pattern in both viral genes. Group 2 isolates (HD, n = 1; AILD, n = B-NHL, n = 1; tonsils of EBV-seropositive children, n = 9; IM, n = 20 showed a nucleotide change at position 49095 in the EBNA-2 gene, leading to an amino acid substitution (Pro-->Ser), and EBV type-2 sequences in the EBER region. EBV type-1 isolates that fall into group 3 (AILD, n = 3; HD, n = 1; B-NHL, n = 4; gastric carcinoma, n = 2; IM, n = 6; severe chronic active EBV infection, n = 1) were characterized by typical nucleotide changes and a 3-bp insertion (CTC; extra Leu residue) in the EBNA-2 gene and an EBV type-2-specific sequence pattern in the EBER region. These EBV type-1 variant strains may represent the most prevalent circulating EBV type-1 strains in the exposed population and seem not to be restricted to a certain EBV-associated disease or tumor type. However, analysis of more EBV isolates from benign and malignant lesions must show whether more EBV type-1 substrains exist in vivo.
Schuster
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Children's Hospital, University of Würzburg, Germany.
Ott
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Seidenspinner
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S
Kreth
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HW
D001483:Base Sequence; D002648:Child; D017931:DNA Primers / Q000737:chemistry; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D005796:Genes; D006566:Herpesviridae Infections / Q000382:microbiology*; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007119:Immunoblastic Lymphadenopathy / Q000382:microbiology*; D007244:Infectious Mononucleosis / Q000382:microbiology; D008228:Lymphoma, Non-Hodgkin / Q000382:microbiology*; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012367:RNA, Viral / Q000235:genetics; D013274:Stomach Neoplasms / Q000382:microbiology*; D014412:Tumor Virus Infections / Q000382:microbiology*
D017931:DNA Primers; D004279:DNA, Viral; D012367:RNA, Viral