Important role for the murid herpesvirus 4 ribonucleotide reductase large subunit in host colonization via the respiratory tract.
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.
Gill
Michael B
MB
Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom.
May
Janet S
JS
Colaco
Susanna
S
Stevenson
Philip G
PG
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D006224:Cricetinae; D004279:DNA, Viral / Q000235:genetics; D005814:Genes, Viral; D006566:Herpesviridae Infections / Q000821:virology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016254:Mutagenesis, Insertional; D012137:Respiratory System / Q000821:virology; D018144:Rhadinovirus / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D012264:Ribonucleotide Reductases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014412:Tumor Virus Infections / Q000821:virology; D014774:Virulence / Q000235:genetics / Q000502:physiology; D014779:Virus Replication / Q000235:genetics / Q000502:physiology
D004279:DNA, Viral; D012264:Ribonucleotide Reductases