Identification of an Epstein-Barr virus-coded thymidine kinase.

Littler, Edward; Zeuthen, Jesper; McBride, Alison A.; Sørensen, E Trøst; Powell, Kenneth L.; Walsh-Arrand, J E; Arrand, John R.

doi:10.1002/j.1460-2075.1986.tb04450.x

Cited by 82 publications

(53 citation statements)

References 53 publications

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“…genes 35 and 37) have counterparts on either side of EBV BXLF1 (i.e. BXRF1 and BXLF2), are in accord with direct evidence, presented recently by Littler et al (1986), that BXLF1 encodes a TK.…”

Section: A J Davison and P Taylor (A)supporting

confidence: 88%

Genetic Relations between Varicella-Zoster Virus and Epstein-Barr Virus

Davison

Taylor

1987

Journal of General Virology

108

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SUMMARYVaricella-zoster virus (VZV) and Epstein-Barr virus (EBV) are important human pathogens which belong to different subfamilies of the herpesviruses : the Alpha-and Gammaherpesvirinae, respectively. Computer comparisons of the amino acid sequences of proteins predicted from the published complete VZV and EBV DNA sequences resulted in the detection of EBV counterparts to 29 of the 67 unique VZV genes. Conserved genes were detected only in the UL component of each genome, and are located in three major regions, within which conserved genes are generally colinear. However, the three regions are arranged differently in the two genomes. These results make it possible in principle to propose the functions of EBV genes on the basis of the functions of their VZV counterparts. The data also allow identification of the types of events which may have occurred during divergence of VZV and EBV, as representatives of the Alpha-and Gammaherpesvirinae, from a common ancestor.

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Section: A J Davison and P Taylor (A)supporting

confidence: 88%

Genetic Relations between Varicella-Zoster Virus and Epstein-Barr Virus

Davison

Taylor

1987

Journal of General Virology

108

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“…Whalley, 1988), HSV-1 (Colb6re- Garapin et al, 1979;Enquist et al, 1979;Wilkie et al, 1979;McKnight, 1980;Wagner et al, 1981), HSV-2 (McDougall et al, 1980;Galloway & Swain, 1980;Swain & Galloway, 1983), IBRV (Kit, 1985a;Liu & Manning, 1986;Mittal & Field, 1989), marmoset herpesvirus (MHV) (Otsuka et al, 1981;Otsuka & Kit, 1984), PRV (Kit, 1985a, b) and VZV (Davison & Scott, 1983;, and the gammaherpesviruses Epstein-Barr virus (EBV) (Baer et al, 1984;Littler et al, 1986) and herpesvirus saimiri (HVS) (Honess et al, 1989b). Similarly, the genes encoding the human (Bradshaw & Deininger, 1984) and chicken cytoplasmic TKs (Perucho et al, 1980;Kwoh & Engler, 1984) have also been cloned and sequenced.…”

Section: T--t--mentioning

confidence: 99%

Nucleotide and Predicted Amino Acid Sequences of the Marek's Disease Virus and Turkey Herpesvirus Thymidine Kinase Genes; Comparison with Thymidine Kinase Genes of Other Herpesviruses

Scott¹,

Ross²,

Binns³

1989

Journal of General Virology

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SUMMARYIn this paper we present the nucleotide sequences of the thymidine kinase (TK) genes of two avian herpesviruses : a highly oncogenic strain of Marek's disease virus (MDV strain RBIB) and its serologically related vaccine virus, the herpesvirus of turkeys (HVT strain Fc-126). The predicted coding regions of the two genes are 1029 and 1050 nucleotides respectively, corresponding to polypeptides of 343 and 350 amino acids in length. Putative nucleotide-and nucleoside-binding sites have been identified within the two predicted amino acid sequences. The MDV and HVT TK amino acid sequences exhibit 58-2~ amino acid identity. Comparison with other available herpesvirus TK sequences reveals a greater homology to those of the alphaherpesviruses than to those of the gammaherpesviruses. No overall homology was found when compared with the chicken cytoplasmic TK sequence.

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“…Anti-viral approaches have been developed based on the complex relationship between EBV and these diseases. EBV TK, an early lytic protein encoded by the BXLF1 open reading frame [22,23], plays a major role in most of these anti-EBV strategies. Diseases involving lytic EBV infection, such as HIV-oral hairy leukoplakia, regress when treated with nucleoside analogues [15].…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of the conserved nucleoside-binding sites in the Epstein-Barr virus thymidine kinase

Chen

Chang

et al. 2004

Biochemical Journal

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Thymidine kinase (TK), encoded by EBV (Epstein-Barr virus), is an attractive target for antiviral therapy and provides a novel approach to the treatment of EBV-associated malignancies. Despite the extensive use of nucleoside analogues for the treatment of viral infections and cancer, the structure-function relationship of EBV TK has been addressed rarely. In the absence of any structural information, we sought to identify and elucidate the functional roles of amino acids in the nucleoside-binding site using site-directed mutagenesis. Through alignment with other human herpesviral TK protein sequences, we predicted that certain conserved regions comprise the nucleoside-binding site of EBV TK and, through site-directed mutagenesis, showed significant changes in activity and binding affinity for thymidine of site 3 (-DRH-) and 4 (-VFP-) mutants. For site 3, only mutants D392E (Asp 392 → Glu) and R393H retain activity, indicating that a negative charge is important for Asp 392 and a positive charge is required for Arg 393 . The increased binding affinities of these two mutants for 3 -deoxy-2 ,3 -didehydrothymidine suggest that the two residues are also important for substrate selection. Interestingly, the changed metal-ion usage pattern of D392E reveals that Asp 392 plays multiple roles in this region. His 394 cannot be compensated by other amino acids, also indicating a crucial role. In site 4, the F402Y mutant retains full activity; however, F402S retains only 60 % relative activity. Strikingly, when Phe 402 is substituted with serine residue, the original preferred pyrimidine substrates, such as 3 -azido-3 -deoxythymidine, iododeoxyuridine and β-L-5-iododioxolane uracil (L-form substrate), have decreased competitiveness with thymidine, suggesting that Phe 402 plays a crucial role in substrate specificity and that the aromatic ring is important for function.

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Identification of an Epstein-Barr virus-coded thymidine kinase.

Cited by 82 publications

References 53 publications

Genetic Relations between Varicella-Zoster Virus and Epstein-Barr Virus

Genetic Relations between Varicella-Zoster Virus and Epstein-Barr Virus

Nucleotide and Predicted Amino Acid Sequences of the Marek's Disease Virus and Turkey Herpesvirus Thymidine Kinase Genes; Comparison with Thymidine Kinase Genes of Other Herpesviruses

Identification and characterization of the conserved nucleoside-binding sites in the Epstein-Barr virus thymidine kinase

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