title: Polymorphisms of the region of the Epstein-Barr virus genome which disrupts latency.
abstract: The nucleotide sequence of the portion of naturally occurring defective EBV (HR-1) DNA (designated het DNA) which is responsible for disruption of EBV latency has been determined and compared with the regions of the standard HR-1 viral genome from which it was derived. This rearranged 2.7-kbp DNA fragment represented an apparently nonhomologous recombination between sequences found in the BamHI W and BamHI Z fragments of the standard HR-1 genome. Only one intact open reading frame, comparable to standard HR-1 BZLF1, was present within this 2.7 kbp. No new open reading frames were created by the recombination. The BZLF1 sequence and predicted polypeptide products of standard HR-1 and het DNA were compared to B95-8 EBV. If an unspliced version of BZLF1 is used, the carboxy end of the BZLF1 polypeptides would differ considerably, principally due to an identical 28-bp insertion in both standard HR-1 and het BZLF1 relative to B95-8. However, if both virus strains use the same mRNA splicing strategy, the BZLF1 products from HR-1 and B95-8 would be similar, though distinguished by seventeen 1-bp differences which would result in nine amino acid changes. Both unspliced and spliced versions of het BZLF1 had five amino acid changes by comparison to standard HR-1 BZLF1. Differences in predicted secondary structure were found, consistent with dissimilar electrophoretic mobility of the polypeptide products. The amino acid differences between the BZLF1 polypeptide products of HR-1, het DNA, and B95-8 virus are all compatible with the creation of a protein which would function similarly to disrupt EBV latency. The differences in these polypeptides may account for some of the variation in the level of biologic activity of the BZLF1 products of different EBV strains. However, the major difference in activity between standard HR-1 and HR-1 het virus to disrupt EBV latency appears to be due to up-regulation of expression of het BZLF1 due to juxtaposition of BamHI W sequences upstream of het BZLF1.
authors.affiliation: Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06510.
authors.forename: H B
authors.initials: HB
authors.lastname: Jenson
authors.forename: G
authors.initials: G
authors.lastname: Miller
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D004279:DNA, Viral / Q000235:genetics; D003673:Defective Viruses / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D005814:Genes, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000472:pathogenicity; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D014764:Viral Proteins / Q000235:genetics; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D014764:Viral Proteins