DEOXYURIDINE METABOLISM IN HERPES LABIALIS

单纯疱疹病毒（HS）1型是疱疹的病原体 唇和HSV感染之间存在相关性， 某些肿瘤性疾病的发展。 HSV诱导约50 多肽，其中一些具有酶活性，在允许的情况下， 被感染的细胞 然而，除了HSV编码的DNA聚合酶， 这些多肽在HSV复制、重组转化和 延迟是未知的。 本研究的目的是确定 HSV特异性脱氧尿苷三磷酸核苷酸水解酶的功能 （dUTR）在HSV复制和重组中的作用，并确定 dUTR在影响特异性抗病毒药物活性中的潜在作用 用于治疗HSV引起的感染的药物。 的影响 病毒感染者HSV DNA中脱氧尿苷（dUdr）掺入增加 复制、重组和诱变将使用HSV dUTR活性缺陷的突变体。 我们将量化 掺入这些突变体DNA中的dUdr的量， 确定dUdr掺入DNA的增加对 病毒DNA的感染性，确定这些突变频率 脱氧尿苷（-）突变体溴脱氧尿苷和膦酰乙酸，测定 dUTR（-）突变体中相对于DNA的重组频率 聚合酶和胸苷激酶结构基因，我们将确定 HSV编码的dUTR的结构基因的图谱定位。 我们将 还确定了HSV特异性dUTR在影响 通过在体内测定特定抗病毒化合物的活性， dUTR（-）突变体对特异性胸苷（脱氧尿苷）的敏感性 类似物，并通过体外测定 这些类似物可以作为细胞和/或HSV的替代底物 特定dUTPases。 这些研究将不仅提供一个insite到 HSV特异性dUTR在病毒复制中的功能，但它们应该 提供一种机制，允许代理人的合理发展 可以用于抗病毒治疗。 这些研究也可能 证明dUTR-突变体可用于开发筛选 用于检测潜在抗病毒药物的试验。

Herpes-simplex virus (HS) type 1 is the etiological agent of herpes labialis and there is a correlation between HSV infections and the development of certain neoplastic diseases. HSV induces approximately 50 polypeptides, some of which possess enzymatic activity, in permissively infected cells. However except for the HSV encoded DNA polymerase the role of these polypeptides in HSV replication, recombination transformation, and latency is unknown. The goals of this research are to determine the function of a HSV specified deoxyuridine triphosphate nucleotidohydrolase (dUTPase) in HSV replication and recombination and to determine the dUTPase's potential role in affecting the activity of specific antiviral agents used in the treatment of infections caused by HSV. The effect of increased deoxyuridine (dUdr) incorporation into HSV DNA on viral replication, recombination and mutagenesis will be determined using HSV mutants which are defective in dUTPase activity. We will quantitate the amount of dUdr that is incorporated into the DNA of these mutants, determine what effect increased dUdr incorporation into the DNA has on the infectivity of the viral DNA, determine the mutation frequency in these dUTPase(-) mutants to bromodeoxyuridine and phosphonoacetic acid, determine the recombination frequency in the dUTPase(-) mutants relative to the DNA polymerase and thymidine kinase structural genes and we will determine the map location of the structural gene for the HSV encoded dUTPase. We will also determine the potential role of the HSV specified dUTPase in affecting the activity of specific antiviral compounds by determining in vivo the sensitivity of the dUTPase(-) mutants to specific thymidine (deoxyuridine) analogs and by determining in vitro whether the triphosphate derivitives of these analogs can act as alternative substrates for the cellular and/or HSV specified dUTPases. These studies will not only provide an insite into the function of the HSV-specified dUTPase in virus replication but they should provide a mechanism that will allow for the rational development of agents that can be employed for antiviral therapy. Also these studies may demonstrate that the dUTPase- mutants can be use for developing a screening test for the detection of potential antiviral agents.