Epstein-Barr virus gene expression in interferon-treated cells. Implications for the regulation of protein synthesis and the antiviral state.
This paper presents data on the effects of interferon treatment on Epstein-Barr virus (EBV) gene expression in latently infected Daudi Burkitt's lymphoma cells, and reviews the possible role of viral gene products in the regulation of translation. In Daudi cells the main virally coded RNAs are the small untranslated RNAs EBER-1 and EBER-2, two mRNAs for the DNA binding protein EBNA-1, and a number of small RNAs containing sequences from the BamHI W repeat region of the viral genome. Interferon treatment does not change the qualitative pattern of EBV gene expression but decreases the levels of the EBNA-1 mRNAs. The chromatographic behaviour of EBV-encoded RNAs on CF11-cellulose indicates that many contain double-stranded regions; these RNAs co-purify with RNA that activates the interferon-induced, dsRNA-sensitive protein kinase DAI. Computer analysis indicates that the exons transcribed from the BamHI W repeats have the potential for formation of very stable secondary structures. Many viruses can counteract the inhibition of protein synthesis mediated by the DAI-catalysed phosphorylation of initiation factor eIF-2 and our data suggest that the small RNA EBER-1 may fulfil this function in the EBV system. During the infection and immortalization of B lymphocytes by EBV the synthesis of large amounts of EBER-1 RNA might thus allow the virus to circumvent one of the interferon-mediated mechanisms of host cell defence.
Clarke
P A
PA
Department of Cellular and Molecular Sciences, St. George's Hospital Medical School, London, U.K.
Sharp
N A
NA
Arrand
J R
JR
Clemens
M J
MJ
D000199:Actins / Q000235:genetics; D000956:Antigens, Viral / Q000235:genetics; D001483:Base Sequence; D002051:Burkitt Lymphoma; D002151:Calorimetry; D002460:Cell Line; D019309:Epstein-Barr Virus Nuclear Antigens; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D005814:Genes, Viral / Q000187:drug effects*; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D015183:Restriction Mapping
D000199:Actins; D000956:Antigens, Viral; D019309:Epstein-Barr Virus Nuclear Antigens; D007370:Interferon Type I; D012333:RNA, Messenger; D012367:RNA, Viral