The gammaherpesvirus thymidine kinase

伽马疱疹病毒胸苷激酶

• 批准号: G0701185/1
• 负责人: Philip Stevenson
• 金额: $ 131.16万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0701185%2F1
• 关键词: gammaherpesvirus; thymidine; kinase

Herpesviruses are ubiquitous infections and cause many clinical problems in immunosuppressed patients. The most effective treatment to date has been anti-viral drugs such as aciclovir, which exploit a viral enzyme called thymidine kinase (TK). The gamma-herpesviruses have this enzyme, but it is a much weaker enzyme than that of alpha-herpesviruses, against which aciclovir was developed. We suspect that the gamma-herpesvirus TK has different functions, and might therefore best be attacked through different types of drugs.The human gamma-herpesviruses only infect primates, making many experiments impractical. We are therefore defining what the gamma-herpesvirus TK does using a related murine virus, called MHV-68. We know that the MHV-68 TK is important for viral replication in mice. We aim now to work out why, specifically whether it works in the same way as the alpha-herpesvirus TK, or whether it has very different functions that would be best inhibited in different ways. By understanding how the MHV-68 TK works, we should be able to provide a basis for effective TK-based therapies in gamma-herpesvirus infections.

疱疹病毒是普遍存在的感染，在免疫抑制患者中引起许多临床问题。迄今为止最有效的治疗方法是阿昔洛韦等抗病毒药物，它利用一种称为胸苷激酶（TK）的病毒酶。 γ-疱疹病毒具有这种酶，但它比α-疱疹病毒的酶弱得多，阿昔洛韦是针对α-疱疹病毒开发的。我们怀疑γ-疱疹病毒TK具有不同的功能，因此最好通过不同类型的药物来攻击。人类γ-疱疹病毒仅感染灵长类动物，使得许多实验不切实际。因此，我们使用一种相关的鼠科病毒（称为 MHV-68）来定义 γ-疱疹病毒 TK 的作用。我们知道 MHV-68 TK 对于小鼠体内的病毒复制很重要。我们现在的目标是找出原因，特别是它是否以与α-疱疹病毒TK相同的方式起作用，或者它是否具有非常不同的功能，可以通过不同的方式得到最好的抑制。通过了解 MHV-68 TK 的工作原理，我们应该能够为基于 TK 的有效治疗 γ-疱疹病毒感染的疗法提供基础。