title: Mechanisms of temperature sensitivity of attenuated Urabe mumps virus.
abstract: Temperature sensitivity is a phenotype often associated with attenuation of viruses. Previously, we purified several mumps variants from an incompletely attenuated Urabe strain live attenuated vaccine. Here we characterize one isolate that is sensitive to growth at high temperature. This virus was attenuated in a small animal model of mumps virulence, and we identified unique coding substitutions in the hemagglutinin-neuraminidase (HN), the viral polymerase (L) gene, and a non-coding substitution close to the anti-genome promoter sequences. At the non-permissive temperature, transcription of viral mRNAs and production of the replication intermediate were reduced compared to events at the permissive temperature and to a non-ts virulent Urabe virus. As well, synthesis of viral proteins was also reduced at the higher temperature. While the actual sequence substitutions in the ts virus were unique, the pattern of substitutions in HN, L and genome end sequences is similar to another attenuated Urabe virus previously described by us.
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, K1H 8M5, Canada. Electronic address: sburk089@uottawa.ca.
authors.forename: Stephanie C Burke
authors.initials: SCB
authors.lastname: Schinkel
authors.affiliation: Food and Drug Administration (FDA), Center for Biologics Evaluation and Research (CBER), OVRR, DVP, 10903 New Hampshire Avenue, Bldg 52/72, Silver Spring, MD, 20993, United States. Electronic address: rubins@ceber.FDA.gov.
authors.forename: Steven
authors.initials: S
authors.lastname: Rubin
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, K1H 8M5, Canada. Electronic address: kwright@uottawa.ca.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Wright
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D014644:Genetic Variation; D009109:Mumps virus / Q000145:classification / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012367:RNA, Viral; D013696:Temperature; D014158:Transcription, Genetic; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics
chemical_list: D012367:RNA, Viral; D014764:Viral Proteins
keywords: Attenuation; Mumps virus; Replication; Temperature sensitivity; Transcription