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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.
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页码:10937 / 10942
页数:6
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