2 DISTINCT LOCI CONFER RESISTANCE TO ACYCLOGUANOSINE IN HERPES-SIMPLEX VIRUS TYPE-1
2 DISTINCT LOCI CONFER RESISTANCE TO ACYCLOGUANOSINE IN HERPES-SIMPLEX VIRUS TYPE-1
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DOI：
10.1073/pnas.77.4.2265
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发表时间：
1980-01-01
期刊：
影响因子：
--
通讯作者：
SCHAFFER, PA
中科院分区：
文献类型：
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作者：
COEN, DM;SCHAFFER, PA
两个不同的基因座，赋予耐药的无环鸟苷（无环郭）在单纯疱疹病毒1型被确定。第1个基因座是病毒特异性胸苷激酶（TK）基因。降低TK活性的突变也使病毒对无环郭产生耐药性，并且耐药性水平对应于TK活性的降低。由于TK表达缺陷导致的无环-Guo抗性相对于野生型表型、无环-Guo敏感性（ACG）是隐性的。这个位点被称为ACGr-TK。第二个基因座由突变体PAAr 5的性质定义，PAAr 5对acyclo-Guo和膦酰基乙酸（PAA）具有抗性，但表现出野生型TK活性。PAAr 5中的无环-Guo抗性基因座可通过重组与ACGr-TK突变分离。PAAr 5和ACGr-TK突变体可以相互补充，产生药物敏感的基因产物，在无环郭的存在下导致生长抑制。由PAAr 5赋予的无环-Guo抗性表现为好像它与野生型表型共显性。该第二个无环-Guo-抗性基因座与指定对PAA的抗性的突变密切相关。对PAA的耐药性被认为是由病毒DNA聚合酶基因突变引起的。因此，ACGr和帕尔基因座的紧密连锁表明，对两种药物的耐药性是由突变的DNA聚合酶指定的。这个第二个位点被称为ACGr-PAA。
Two distinct loci that confer resistance to acycloguanosine (acyclo-Guo) in herpes simplex virus type 1 were identified. The 1st locus is the gene for the virus-specific thymidine kinase (TK). Mutations that decrease TK activity also render the virus resistant to acyclo-Guo, and the level of resistance corresponds to the decrease in TK activity. acyclo-Guo resistance due to defective TK expression is recessive to the wild-type phenotype, acyclo-Guo-sensitive (ACGs). This locus was called ACGr-TK. The 2nd locus is defined by the properties of a mutant, PAAr5, which is resistant to acyclo-Guo and to phosphonoacetic acid (PAA) yet exhibits wild-type TK activity. The acyclo-Guo-resistant locus in PAAr5 is separable from ACGr-TK mutations by recombination. PAAr5 and ACGr-TK mutants can complement each other, producing drug-sensitive gene products which result in growth inhibition in the presence of acyclo-Guo. The acyclo-Guo resistance conferred by PAAr5 behaves as though it were codominant with the wild-type phenotype. This 2nd acyclo-Guo-resistance locus is closely linked to the mutation specifying resistance to PAA. Resistance to PAA is thought to result from mutations in the gene for viral DNA polymerase. Thus, the close linkage of the ACGr and PAAr loci suggests that resistance to both drugs is specified by a mutant DNA polymerase. This 2nd locus was termed ACGr-PAA.