鼠疱疹病毒 4 核糖核苷酸还原酶大亚基在通过呼吸道定植宿主中的重要作用。
Important role for the murid herpesvirus 4 ribonucleotide reductase large subunit in host colonization via the respiratory tract.
机构信息
Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom.
出版信息
J Virol. 2010 Oct;84(20):10937-42. doi: 10.1128/JVI.00828-10. Epub 2010 Jul 28.
Abstract
Viral enzymes that process small molecules provide potential chemotherapeutic targets. A key constraint-the replicative potential of spontaneous enzyme mutants-has been hard to define with human gammaherpesviruses because of their narrow species tropisms. Here, we disrupted the murid herpesvirus 4 (MuHV-4) ORF61, which encodes its ribonucleotide reductase (RNR) large subunit. Mutant viruses showed delayed in vitro lytic replication, failed to establish infection via the upper respiratory tract, and replicated to only a very limited extent in the lower respiratory tract without reaching lymphoid tissue. RNR could therefore provide a good target for gammaherpesvirus chemotherapy.
摘要
病毒小分子加工酶为潜在的化学治疗靶标。一个关键的限制因素是自发酶突变体的复制潜力，这很难用人类γ疱疹病毒来定义，因为它们的物种嗜性很窄。在这里，我们破坏了鼠疱疹病毒 4（MuHV-4）的 ORF61，该基因编码其核苷酸还原酶（RNR）的大亚基。突变病毒的体外裂解复制延迟，不能通过上呼吸道建立感染，在下呼吸道仅有限复制而不能到达淋巴组织。因此，RNR 可以为 γ疱疹病毒的化学治疗提供一个很好的靶标。
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