Role of mutations identified in ORFs M56 (terminase), M70 (primase) and M98 (endonuclease) in the temperature-sensitive phenotype of murine cytomegalovirus mutant tsm5

Twenty-six non-synonymous and synonymous mutations have been identified in the temperature-sensitive ( ts) mutant ( tsm5) of the K181 (Birmingham) variant of murine cytomegalovirus that is deficient in DNA synthesis, processing and packaging at the non-permissive temperature and produces undetectabl...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2009-09, Vol.392 (1), p.114-122
Main Authors: Timoshenko, Olga, Al-Ali, Abdulaziz, Martin, Brian A.B., Sweet, Clive
Format: Article
Language:English
Subjects:
Animals
Attenuated
Bacterial artificial chromosomes
Base Sequence
Chromosomes, Artificial, Bacterial - genetics
Cysteine
DNA biosynthesis
DNA Primase - genetics
DNA, Viral - biosynthesis
DNA, Viral - genetics
Endodeoxyribonucleases - genetics
Endonuclease
Endonucleases - genetics
Genes, Viral
Genetic Variation
M56
M70
M98
Mice
Mice, Inbred BALB C
Murine cytomegalovirus
Muromegalovirus - enzymology
Muromegalovirus - genetics
Muromegalovirus - physiology
Mutation
Nuclease
Open Reading Frames
Packaging
Phenotype
Primase
Reversion
Temperature
Temperature effects
Temperature-sensitive mutant
Terminase
Tissue Culture Techniques
tsm5
Tyrosine
Virus Replication
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Summary:Twenty-six non-synonymous and synonymous mutations have been identified in the temperature-sensitive ( ts) mutant ( tsm5) of the K181 (Birmingham) variant of murine cytomegalovirus that is deficient in DNA synthesis, processing and packaging at the non-permissive temperature and produces undetectable levels of infectious virus in mice. Non-synonymous mutations identified in the M70 (primase), M56 (terminase) and M98 (nuclease) ORFs were introduced individually and in combination into the K181 (Perth) variant using BAC technology to examine their role in the ts phenotype. The M56 (G439R) and M98 (P324S) mutations had no evident role in the ts phenotype. However, the C890Y M70 mutation alone and in combination with the M56 and/or M98 mutations rendered the virus ts, unable to replicate in mice and highly defective in DNA synthesis. Reversion of the tyrosine mutation to cysteine or introduction of C890M (experimentally) or C890S (naturally) restored the wt phenotype.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2009.06.049