scholarly journals A hybrid herpesvirus infectious vector based on Epstein-Barr virus and herpes simplex virus type 1 for gene transfer into human cells in vitro and in vivo.

1996 ◽  
Vol 70 (12) ◽  
pp. 8422-8430 ◽  
Author(s):  
S Wang ◽  
J M Vos
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Gene Transfer ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Epstein Barr ◽  
Simplex Virus

scholarly journals The Epstein-Barr Virus Thymidine Kinase Does Not Phosphorylate Ganciclovir or Acyclovir and Demonstrates a Narrow Substrate Specificity Compared to the Herpes Simplex Virus Type 1 Thymidine Kinase

1998 ◽  
Vol 42 (11) ◽  
pp. 2923-2931 ◽  
Author(s):  
Erik A. Gustafson ◽  
Antoinette C. Chillemi ◽  
David R. Sage ◽  
Joyce D. Fingeroth
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Substrate Specificity ◽  
Thymidine Kinase ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Epstein Barr ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT The Epstein-Barr virus (EBV) thymidine kinase (TK) was expressed in mammalian 143B TK− cells to investigate its substrate specificity. The herpes simplex virus type 1 (HSV-1) TK was similarly expressed for comparison. Both viral TKs conferred a TK+ phenotype on 143B TK− cells. The nucleoside analog ganciclovir (GCV) did not affect the growth of 143B EBV TK or 143B TK− cells but effectively killed 143B HSV-1 TK cells. Furthermore, lysates of 143B EBV TK cells could not phosphorylate GCV, which was confirmed by high-performance liquid chromatography. EBV TK, HSV-1 TK, and EBV TK N−, a truncated EBV TK missing 243 N-terminal amino acids, were purified as fusion proteins expressed in bacteria, and all had TK activity. In addition, EBV TK was observed to have a thymidylate kinase activity but could not phosphorylate GCV, acyclovir, or 2′-deoxycytidine. In competition assays, only nucleoside analogs of thymidine significantly inhibited thymidine phosphorylation by EBV TK, with the following rank order: 5-bromodeoxyuridine > zidovudine > stavudine > sorivudine. These results demonstrate that EBV TK substrate specificity is narrower than those of alphaherpesvirus TKs and that thymidine analogs may be the most suitable nucleoside antivirals to target the enzyme. Clinical implications for gammaherpesviruses are discussed.

scholarly journals Antiherpesvirus Activities of Two Novel 4′-Thiothymidine Derivatives, KAY-2-41 and KAH-39-149, Are Dependent on Viral and Cellular Thymidine Kinases

2014 ◽  
Vol 58 (8) ◽  
pp. 4328-4340 ◽  
Author(s):  
Natacha Coen ◽  
Sophie Duraffour ◽  
Kazuhiro Haraguchi ◽  
Jan Balzarini ◽  
Joost J. van den Oord ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antiviral Activity ◽  
Epstein Barr Virus ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Epstein Barr ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACTThe emergence of drug-resistant herpesviruses represents a significant problem in clinical practice, primarily in immunocompromised patients. Furthermore, effective antiviral therapies against gammaherpesvirus-associated diseases are lacking. Here, we present two thiothymidine derivatives, KAY-2-41 and KAH-39-149, with different spectra of antiviral activity from those of the reference antiherpetic drugs, showing inhibitory activities against herpes simplex virus, varicella-zoster virus (VZV), and particularly against Epstein-Barr virus, with high selectivityin vitro. While KAY-2-41- and KAH-39-149-resistant herpesviruses were found to harbor mutations in the viral thymidine kinase (TK), these mutations conferred only low levels of resistance to these drugs but high levels to other TK-dependent drugs. Also, antiviral assays in HeLa TK-deficient cells showed a lack of KAY-2-41 and KAH-39-149 activities against herpes simplex virus 1 (HSV-1) and HSV-2 TK-deficient mutants. Furthermore, enzymatic TK assays showed the ability of HSV-1 TK, VZV TK, and cellular TK1 and TK2 to recognize and phosphorylate KAY-2-41 and KAH-39-149. These results demonstrate that the compounds depend on both viral and host TKs to exert antiviral activity. Additionally, the antiviral efficacy of KAH-39-149 proved to be superior to that of KAY-2-41 in a mouse model of gammaherpesvirus infection, highlighting the potential of this class of antiviral agents for further development as selective therapeutics against Epstein-Barr virus.

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