Important Role for the Murid Herpesvirus 4 Ribonucleotide Reductase Large Subunit in Host Colonization via the Respiratory Tract

被引:16
作者
Gill, Michael B. [1 ]
May, Janet S. [1 ]
Colaco, Susanna [1 ]
Stevenson, Philip G. [1 ]
机构
[1] Univ Cambridge, Dept Pathol, Div Virol, Cambridge CB2 1QP, England
基金
英国医学研究理事会; 英国惠康基金;
关键词
VIRAL GENE-EXPRESSION; IN-VIVO; KAPOSIS-SARCOMA; GAMMAHERPESVIRUS-68; REPLICATION; INFECTION; LATENCY; CELLS; MICE; IDENTIFICATION;
D O I
10.1128/JVI.00828-10
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 gammaher-pesviruses 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.
引用
收藏
页码:10937 / 10942
页数:6
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