Thymidine kinase with altered substrate specificity of acyclovir resistant varicella-zoster virus.

Biken journal Pub Date : 1986-03-01
K Shiraki, T Ogino, K Yamanishi, M Takahashi
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Abstract

The acyclovir resistant mutant of varicella-zoster virus ACV-R (A 8) induced the same level of thymidine kinase activity in infected cells as the parent Kawaguchi strain. However, it induced less deoxycytidine kinase activity and did not induce phosphorylating activity for the nucleotide analogue, 9-(2 hydroxy-ethoxymethyl)-guanine-(acyclovir). Another acyclovir resistant mutant, ACV-R (A 4), which is cross-resistant to phosphonoacetate and is thought to be a viral DNA polymerase mutant, induced the same level of phosphorylating activities for thymidine, deoxycytidine and acyclovir as the parent strain. The altered substrate specificity of thymidine kinase induced by ACV-R (A 8) is concluded to confer resistance to acyclovir on ACV-R (A 8).

无环鸟苷耐药水痘-带状疱疹病毒底物特异性改变的胸苷激酶
水痘-带状疱疹病毒ACV-R (a8)抗无环鸟苷突变体在感染细胞中诱导的胸苷激酶活性与亲本川口毒株相同。然而,它诱导较少的脱氧胞苷激酶活性,并且不会诱导核苷酸类似物9-(2羟基-乙氧基甲基)-鸟嘌呤-(无环鸟苷)的磷酸化活性。另一种抗阿昔洛韦突变体ACV-R (4a)对磷酸醋酸酯具有交叉抗性,被认为是一种病毒DNA聚合酶突变体,诱导胸苷、脱氧胞苷和阿昔洛韦的磷酸化活性与亲本菌株相同。ACV-R (a8)诱导胸苷激酶底物特异性的改变被认为是ACV-R (a8)对阿昔洛韦产生耐药性的原因。
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