Genome Diversity of Epstein-Barr Virus from Multiple Tumor Types and Normal Infection

Epstein-Barr virus (EBV) infects most of the world’s population and is causally associated with several human cancers, but little is known about how EBV genetic variation might influence infection or EBV-associated disease. There are currently no published wild-type EBV genome sequences from a healthy individual and very few genomes from EBV-associated diseases. We have sequenced 71 geographically distinct EBV strains from cell lines, multiple types of primary tumor, and blood samples and the first EBV genome from the saliva of a healthy carrier. We show that the established genome map of EBV accurately represents all strains sequenced, but novel deletions are present in a few isolates. We have increased the number of type 2 EBV genomes sequenced from one to 12 and establish that the type 1/type 2 classification is a major feature of EBV genome variation, defined almost exclusively by variation of EBNA2 and EBNA3 genes, but geographic variation is also present. Single nucleotide polymorphism (SNP) density varies substantially across all known open reading frames and is highest in latency-associated genes. Some T-cell epitope sequences in EBNA3 genes show extensive variation across strains, and we identify codons under positive selection, both important considerations for the development of vaccines and T-cell therapy. We also provide new evidence for recombination between strains, which provides a further mechanism for the generation of diversity. Our results provide the first global view of EBV sequence variation and demonstrate an effective method for sequencing large numbers of genomes to further understand the genetics of EBV infection

Serological and molecular screening for viruses in blood donors from Ntcheu, Malawi: High prevalence of HIV-1 subtype C and of markers of hepatitis B and C viruses

The prevalence of antibodies to human immunodeficiency virus type 1 (HIV-1), hepatitis C virus (HCV), human T lymphotropic virus I (HTLV-1), and hepatitis B (HBV) surface antigen (HBsAg) was determined in blood donors from Ntcheu, Malawi. Each donation was also screened for HIV-1 RNA and HCV RNA. Among 159 blood donations, the prevalence of HIV-1 infection was 10.7%, 8.1% for HBV carriage, 6.8% for anti-HCV, and 2.5% for anti-HTLV-1. HIV-1/HTLV-1 and HIV-1/ HCV dual infections were observed in 1.2% of the donations. Consequently, 13% of blood donors from Ntcheu should be deferred for retroviral infections and 15% for hepatitis viral infections. Sequence analyses of the HIV-1 strains revealed a relatively homogeneous circulation of subtype C viruses in Malawi. These findings confirm the high endemicity of blood-borne viruses in Malawi and the need for a sensitive viral screening of blood donations to improve blood safety. © 2001 Wiley-Liss, Inc.link_to_subscribed_fulltex

Comparative analysis of the expression of the Epstein-Barr virus (EBV) anti-apoptotic gene BHRF1 in nasopharyngeal carcinoma and EBV-related lymphoid diseases

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EB virus-encoded RNAs are recognized by RIG-I and activate signaling to induce type I IFN

Epstein–Barr virus (EBV)-encoded small RNAs (EBERs) are nonpolyadenylated, untranslated RNAs, exist most abundantly in latently EBV-infected cells, and are expected to show secondary structures with many short stem–loops. Retinoic acid-inducible gene I (RIG-I) is a cytosolic protein that detects viral double-stranded RNA (dsRNA) inside the cell and initiates signaling pathways leading to the induction of protective cellular genes, including type I interferons (IFNs). We investigated whether EBERs were recognized by RIG-I as dsRNA. Transfection of RIG-I plasmid induced IFNs and IFN-stimulated genes (ISGs) in EBV-positive Burkitt's lymphoma (BL) cells, but not in their EBV-negative counterparts or EBER-knockout EBV-infected BL cells. Transfection of EBER plasmid or in vitro-synthesized EBERs induced expression of type I IFNs and ISGs in RIG-I-expressing, EBV-negative BL cells, but not in RIG-I-minus counterparts. EBERs activated RIG-I's substrates, NF-κB and IFN regulatory factor 3, which were necessary for type I IFN activation. It was also shown that EBERs co-precipitated with RIG-I. These results indicate that EBERs are recognized by RIG-I and activate signaling to induce type I IFN in EBV-infected cells