title: Gene-specific contributions to mumps virus neurovirulence and neuroattenuation.
abstract: Mumps virus (MuV) is highly neurotropic and was the leading cause of aseptic meningitis in the Western Hemisphere prior to widespread use of live attenuated MuV vaccines. Due to the absence of markers of virus neuroattenuation and neurovirulence, ensuring mumps vaccine safety has proven problematic, as demonstrated by the occurrence of aseptic meningitis in recipients of certain vaccine strains. Here we examined the genetic basis of MuV neuroattenuation and neurovirulence by generating a series of recombinant viruses consisting of combinations of genes derived from a cDNA clone of the neurovirulent wild-type 88-1961 strain (r88) and from a cDNA clone of the highly attenuated Jeryl Lynn vaccine strain (rJL). Testing of these viruses in rats demonstrated the ability of several individual rJL genes and gene combinations to significantly neuroattenuate r88, with the greatest effect imparted by the rJL nucleoprotein/matrix protein combination. Interestingly, no tested combination of r88 genes, including the nucleoprotein/matrix protein combination, was able to convert rJL into a highly neurovirulent virus, highlighting mechanistic differences between processes involved in neuroattenuation and neurovirulence.
authors.affiliation: United States Food and Drug Administration, CBER, OVRR, DVP, 8800 Rockville Pike, Building 29A, HFM 460, Room 2C20, Bethesda, MD 20892, USA. christian.sauder@fda.hhs.gov
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Sauder
authors.forename: Cheryl X
authors.initials: CX
authors.lastname: Zhang
authors.forename: Laurie
authors.initials: L
authors.lastname: Ngo
authors.forename: Kellie
authors.initials: K
authors.lastname: Werner
authors.forename: Ken
authors.initials: K
authors.lastname: Lemon
authors.forename: W Paul
authors.initials: WP
authors.lastname: Duprex
authors.forename: Tahir
authors.initials: T
authors.lastname: Malik
authors.forename: Kathryn
authors.initials: K
authors.lastname: Carbone
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rubin
mesh_terms: D000818:Animals; D001288:Attention; D002490:Central Nervous System / Q000821:virology*; D002522:Chlorocebus aethiops; D005814:Genes, Viral; D009109:Mumps virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014709:Vero Cells; D014774:Virulence; D014779:Virus Replication