Distinctive effects of the Epstein-Barr virus family of repeats on viral latent gene promoter activity and B-lymphocyte transformation.
The Epstein-Barr virus (EBV), a human B-lymphotropic gamma herpesvirus, contains multiple repetitive sequences within its genome. A group of repetitive sequences, known as the family of repeats (FR), contains multiple binding sites for the viral trans-acting protein EBNA-1. The FR sequences are important for viral genome maintenance and for the regulation of the promoter involved in viral latent gene expression. It has been reported that a palindromic sequence with a putative secondary structure exists at the 3' end of the FR in the genome of the EBV B95-8 strain and that this palindromic sequence has been deleted from the FR of the commonly used EBV miniplasmids. For the first time, we cloned an EBV B95-8 DNA fragment containing the full-length FR, which enabled us to examine the functional difference between full-length and deleted FRs. The full-length FR, like the deleted FR, functioned as a transcriptional enhancer of the viral latent gene promoter, but that transactivation was significantly attenuated in the case of the full-length FR. No significant enhancement of replication was observed when the deleted FR was replaced with the full-length FR in an EBV miniplasmid. By contrast, when the same set of FR sequences were tested in the context of the complete EBV genome, the full-length FR resulted in more-efficient B-cell transformation than the deleted FR. We propose that the presence of the full-length FR contributes to the precise regulation of the viral latent promoter and increases the efficiency of B-cell transformation.
Ali
Ahmed K M
AK
Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo, Japan.
Saito
Satoru
S
Shibata
Sachiko
S
Takada
Kenzo
K
Kanda
Teru
T
D001402:B-Lymphocytes / Q000821:virology*; D002472:Cell Transformation, Viral; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D055029:Inverted Repeat Sequences; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid / Q000502:physiology*; D014763:Viral Matrix Proteins / Q000235:genetics*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D014763:Viral Matrix Proteins; C417029:EBV-encoded nuclear antigen 1