The gammaherpesvirus thymidine kinase
The gammaherpesvirus thymidine kinase
批准号:
G0701185/1
负责人:
Philip Stevenson
金额:
$131.16万
依托单位:
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
项目状态:
已结题
起止时间:
2008 至 --
中文摘要
疱疹病毒是一种普遍存在的感染,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抗病毒药物,如阿昔洛韦,它利用了一种称为胸苷激酶(TK)的病毒酶。γ-疱疹病毒有这种酶,但它是一种比α-疱疹病毒弱得多的酶,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进行攻击。人类γ-疱疹病毒只感染灵长类动物,使得许多实验不切实际。因此,我们使用一种相关的鼠病毒MHV-68来定义γ-疱疹病毒TK的作用。我们知道MHV-68 TK对小鼠中的病毒复制很重要。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,以不同的方式被最好地抑制。通过了解MHV-68 TK的工作原理,我们应该能够为γ-疱疹病毒感染的有效TK治疗提供基础。
英文摘要
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.
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