DEOXYURIDINE METABOLISM IN HERPES LABIALIS

单纯疱疹病毒（HSV）是多种疱疹的病原体， 包括唇疱疹在内的疾病， HSV感染和某些肿瘤的发展之间的关系 疾病 HSV诱导约50种多肽， 允许感染的细胞，其中一些具有酶 活动 然而，除了HSV诱导的DNA聚合酶外， 和胸苷激酶，很少有人知道的作用，其他 复制或抗病毒化疗中HSV诱导的酶。 本研究的目的是确定HSV是否诱导 脱氧尿苷三磷酸核苷酸水解酶 2.6.1.23）可用作开发的目标站点， 特定的抗病毒化合物，并确定这一作用， 酶在调节化疗药物 特异性抗病毒药物的有效性。 为了做到这一点，我们 计划使用纯化的HSV诱导的和细胞的dUTPases， 阐明有关dUTPases活性位点的特征， 确定这些空间结合特性的差异， 酶，并确定这些酶 dUTPases被各种汞（II）化合物抑制。 我们 将构建，使用插入和定点突变 HSV突变体在dUTR活性上有缺陷， dUTR活性改变。 这些突变体以及野生型 病毒将被用于体内研究，以确定如何变化， 脱氧尿苷（dUrd）池将影响dUTP掺入 HSV DNA，并确定dUTP如何掺入HSV DNA中， DNA影响HSV复制。

Herpes simplex virus (HSV) is the etiological agent of a number of diseases including herpes labialis and there is a correlation between HSV infections and the development of certain neoplastic diseases. HSV induces approximately 50 polypeptides in permissively infected cells and some of these possess enzymatic activity. However, except for the HSV induced DNA polymerase and thymidine kinase, little is known concerning the roles of other HSV-induced enzymes in replication or in antiviral chemotherapy. The goal of this research is to determine whether the HSV induced deoxyuridine triphosphate nucleotidohydrolase (dUTPase, EC 2.6.1.23) can be used as a target site for the development of specific antiviral compounds and to determine what role this enzyme may have in regulating the chemotherapeutic effectiveness of specific antiviral agents. To accomplish this, we plan to use purified HSV induced and cellular dUTPases to elucidate features concerning the active-site of the dUTPases, to determine differences in the steric-binding properties of these enzymes and to determine the mechanism(s) by which these dUTPases are inhibited by various mercury (II) compounds. We will construct, using insertional and site-directed mutagenesis HSV mutants that are defective in dUTPase activity and that have altered dUTPase activity. These mutants as well as wild-type virus will be used in in vivo studies to determine how changes in deoxyuridine (dUrd) pools will effect incorporation of dUTP into HSV DNA and to determine how incorporation of dUTP into the DNA effects HSV replication.