| RRC ID |
43198
|
| Author |
Saijo M, Suzutani T, Mizuta K, Kurane I, Morikawa S.
|
| Title |
Characterization and susceptibility to antiviral agents of herpes simplex virus type 1 containing a unique thymidine kinase gene with an amber codon between the first and the second initiation codons.
|
| Journal |
Arch Virol
|
| Abstract |
A herpes simplex virus type 1 (HSV-1) containing a thymidine (TK) gene with an amber mutation at the 8th position counted from the first AUG codon was isolated from a child with acute gingivostomatitis. The virus was predicted to express a mutant viral translated from the 2nd AUG codon at the 46th amino acid position and consisting of 331 amino acids. The virus was as sensitive to acyclovir (ACV), 5-bromovinyl-2'-deoxyuridine (BVdU), 1-beta-D-arabinofuranosyl-(E)-5-(2-bromovinyl)uracil (BVaraU), and 1-beta-D-arabinofuranosylthymine (araT) as a wild-type HSV-1. The mutant TK showed the same level of TK activity as the wild-type TK at reaction temperatures of 34 degrees C, 37 degrees C and 39 degrees C. ACV, BVdU, BVaraU, and araT inhibited the replication of the TK-deficient and drug-resistant HSV-1 and HSV-2 in 293T cells in which the mutant TK was expressed to the same extent as in cells in which intact HSV-1-TK was expressed, whereas BVdU and BVaraU inhibited the replication of these viruses less strongly in cells in which HSV-2-TK was expressed. It can be concluded that the mutant HSV-1 exists in nature as a variant and possesses the necessary phosphorylation activities to form ACV-monophosphate from ACV, to form BVdU-diphosphate through BVdU-monophosphate from BVdU, and to form BVaraU-diphosphate through BVaraU-monophosphate from BVaraU. These results indicate that the mutant HSV-1-TK with a deletion of the first 45 amino acid residues is phenotypically the same as that of wild-type HSV-1-TK in terms of the phosphorylation activity of TK-associated anti-herpes virus drugs.
|
| Volume |
153(2)
|
| Pages |
303-14
|
| Published |
2008-1-1
|
| DOI |
10.1007/s00705-007-1096-9
|
| PMID |
18066636
|
| MeSH |
Antiviral Agents / pharmacology*
Base Sequence
Cell Line
Child
Codon, Terminator / genetics*
Herpesvirus 1, Human / drug effects*
Herpesvirus 1, Human / genetics*
Herpesvirus 1, Human / isolation & purification
Herpesvirus 2, Human / drug effects
Herpesvirus 2, Human / genetics
Humans
Microbial Sensitivity Tests
Molecular Sequence Data
Sequence Deletion
Stomatitis, Herpetic / virology
Temperature
Thymidine Kinase / genetics*
Thymidine Kinase / metabolism
Viral Plaque Assay
Viral Proteins / genetics*
Viral Proteins / metabolism
Virus Replication / drug effects
|
| IF |
2.243
|
| Times Cited |
7
|
|
WOS Category
|
VIROLOGY
|
| Resource |
| Human and Animal Cells |
143B/TK^(-)neo^(R)(RCB0701) |
