Changes in Mumps Virus Gene Sequence Associated with Variability in Neurovirulent Phenotype

Steven A. Rubin, Georgios Amexis, Mikhail Pletnikov, Jacqueline Vanderzanden, Jeremy Mauldin, Christian Sauder, Tahir Malik, Konstantin Chumakov, Kathryn M. Carbone

Research output: Contribution to journalArticle

Abstract

Mumps virus is highly neurotropic and, prior to widespread vaccination programs, was the major cause of viral meningitis in the United States. Nonetheless, the genetic basis of mumps virus neurotropism and neurovirulence was until recently not understood, largely due to the lack of an animal model. Here, nonneurovirulent (Jeryl Lynn vaccine) and highly neurovirulent (88-1961 wild type) mumps virus strains were passaged in human neural cells or in chicken fibroblast cells with the goal of neuroadapting or neuroattenuating the viruses, respectively. When tested in our rat neurovirulence assay against the respective parental strains, a Jeryl Lynn virus variant with an enhanced propensity for replication (neurotropism) and damage (neurovirulence) in the brain and an 88-1961 wild-type virus variant with decreased neurotropic and neurovirulent properties were recovered. To determine the molecular basis for the observed differences in neurovirulence and neuroattenuation, the complete genomes of the parental strains and their variants were fully sequenced. A comparison at the nucleotide level associated three amino acid changes with enhanced neurovirulence of the neuroadapted vaccine strain: one each in the nucleoprotein, matrix protein, and polymerase and three amino acid changes with reduced neurovirulence of the neuroattenuated wild-type strain: one each in the fusion protein, hemagglutinin-neuraminidase protein, and polymerase. The potential role of these amino acid changes in neurotropism, neurovirulence, and neuroattenuation is discussed.

Original languageEnglish (US)
Pages (from-to)11616-11624
Number of pages9
JournalJournal of Virology
Volume77
Issue number21
DOIs
StatePublished - Nov 2003

Fingerprint

Mumps virus
Viruses
Phenotype
phenotype
nucleotide sequences
Amino Acids
Vaccines
Viral Meningitis
Genes
Proteins
Nucleoproteins
viruses
Hemagglutinins
amino acids
Neuraminidase
Chickens
vaccines
Vaccination
brain damage
Nucleotides

ASJC Scopus subject areas

  • Immunology

Cite this

Rubin, S. A., Amexis, G., Pletnikov, M., Vanderzanden, J., Mauldin, J., Sauder, C., ... Carbone, K. M. (2003). Changes in Mumps Virus Gene Sequence Associated with Variability in Neurovirulent Phenotype. Journal of Virology, 77(21), 11616-11624. https://doi.org/10.1128/JVI.77.21.11616-11624.2003

Changes in Mumps Virus Gene Sequence Associated with Variability in Neurovirulent Phenotype. / Rubin, Steven A.; Amexis, Georgios; Pletnikov, Mikhail; Vanderzanden, Jacqueline; Mauldin, Jeremy; Sauder, Christian; Malik, Tahir; Chumakov, Konstantin; Carbone, Kathryn M.

In: Journal of Virology, Vol. 77, No. 21, 11.2003, p. 11616-11624.

Research output: Contribution to journalArticle

Rubin, SA, Amexis, G, Pletnikov, M, Vanderzanden, J, Mauldin, J, Sauder, C, Malik, T, Chumakov, K & Carbone, KM 2003, 'Changes in Mumps Virus Gene Sequence Associated with Variability in Neurovirulent Phenotype', Journal of Virology, vol. 77, no. 21, pp. 11616-11624. https://doi.org/10.1128/JVI.77.21.11616-11624.2003
Rubin, Steven A. ; Amexis, Georgios ; Pletnikov, Mikhail ; Vanderzanden, Jacqueline ; Mauldin, Jeremy ; Sauder, Christian ; Malik, Tahir ; Chumakov, Konstantin ; Carbone, Kathryn M. / Changes in Mumps Virus Gene Sequence Associated with Variability in Neurovirulent Phenotype. In: Journal of Virology. 2003 ; Vol. 77, No. 21. pp. 11616-11624.
@article{002b78d4746a4e289c604bd3679de1bd,
title = "Changes in Mumps Virus Gene Sequence Associated with Variability in Neurovirulent Phenotype",
abstract = "Mumps virus is highly neurotropic and, prior to widespread vaccination programs, was the major cause of viral meningitis in the United States. Nonetheless, the genetic basis of mumps virus neurotropism and neurovirulence was until recently not understood, largely due to the lack of an animal model. Here, nonneurovirulent (Jeryl Lynn vaccine) and highly neurovirulent (88-1961 wild type) mumps virus strains were passaged in human neural cells or in chicken fibroblast cells with the goal of neuroadapting or neuroattenuating the viruses, respectively. When tested in our rat neurovirulence assay against the respective parental strains, a Jeryl Lynn virus variant with an enhanced propensity for replication (neurotropism) and damage (neurovirulence) in the brain and an 88-1961 wild-type virus variant with decreased neurotropic and neurovirulent properties were recovered. To determine the molecular basis for the observed differences in neurovirulence and neuroattenuation, the complete genomes of the parental strains and their variants were fully sequenced. A comparison at the nucleotide level associated three amino acid changes with enhanced neurovirulence of the neuroadapted vaccine strain: one each in the nucleoprotein, matrix protein, and polymerase and three amino acid changes with reduced neurovirulence of the neuroattenuated wild-type strain: one each in the fusion protein, hemagglutinin-neuraminidase protein, and polymerase. The potential role of these amino acid changes in neurotropism, neurovirulence, and neuroattenuation is discussed.",
author = "Rubin, {Steven A.} and Georgios Amexis and Mikhail Pletnikov and Jacqueline Vanderzanden and Jeremy Mauldin and Christian Sauder and Tahir Malik and Konstantin Chumakov and Carbone, {Kathryn M.}",
year = "2003",
month = "11",
doi = "10.1128/JVI.77.21.11616-11624.2003",
language = "English (US)",
volume = "77",
pages = "11616--11624",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "21",

}

TY - JOUR

T1 - Changes in Mumps Virus Gene Sequence Associated with Variability in Neurovirulent Phenotype

AU - Rubin, Steven A.

AU - Amexis, Georgios

AU - Pletnikov, Mikhail

AU - Vanderzanden, Jacqueline

AU - Mauldin, Jeremy

AU - Sauder, Christian

AU - Malik, Tahir

AU - Chumakov, Konstantin

AU - Carbone, Kathryn M.

PY - 2003/11

Y1 - 2003/11

N2 - Mumps virus is highly neurotropic and, prior to widespread vaccination programs, was the major cause of viral meningitis in the United States. Nonetheless, the genetic basis of mumps virus neurotropism and neurovirulence was until recently not understood, largely due to the lack of an animal model. Here, nonneurovirulent (Jeryl Lynn vaccine) and highly neurovirulent (88-1961 wild type) mumps virus strains were passaged in human neural cells or in chicken fibroblast cells with the goal of neuroadapting or neuroattenuating the viruses, respectively. When tested in our rat neurovirulence assay against the respective parental strains, a Jeryl Lynn virus variant with an enhanced propensity for replication (neurotropism) and damage (neurovirulence) in the brain and an 88-1961 wild-type virus variant with decreased neurotropic and neurovirulent properties were recovered. To determine the molecular basis for the observed differences in neurovirulence and neuroattenuation, the complete genomes of the parental strains and their variants were fully sequenced. A comparison at the nucleotide level associated three amino acid changes with enhanced neurovirulence of the neuroadapted vaccine strain: one each in the nucleoprotein, matrix protein, and polymerase and three amino acid changes with reduced neurovirulence of the neuroattenuated wild-type strain: one each in the fusion protein, hemagglutinin-neuraminidase protein, and polymerase. The potential role of these amino acid changes in neurotropism, neurovirulence, and neuroattenuation is discussed.

AB - Mumps virus is highly neurotropic and, prior to widespread vaccination programs, was the major cause of viral meningitis in the United States. Nonetheless, the genetic basis of mumps virus neurotropism and neurovirulence was until recently not understood, largely due to the lack of an animal model. Here, nonneurovirulent (Jeryl Lynn vaccine) and highly neurovirulent (88-1961 wild type) mumps virus strains were passaged in human neural cells or in chicken fibroblast cells with the goal of neuroadapting or neuroattenuating the viruses, respectively. When tested in our rat neurovirulence assay against the respective parental strains, a Jeryl Lynn virus variant with an enhanced propensity for replication (neurotropism) and damage (neurovirulence) in the brain and an 88-1961 wild-type virus variant with decreased neurotropic and neurovirulent properties were recovered. To determine the molecular basis for the observed differences in neurovirulence and neuroattenuation, the complete genomes of the parental strains and their variants were fully sequenced. A comparison at the nucleotide level associated three amino acid changes with enhanced neurovirulence of the neuroadapted vaccine strain: one each in the nucleoprotein, matrix protein, and polymerase and three amino acid changes with reduced neurovirulence of the neuroattenuated wild-type strain: one each in the fusion protein, hemagglutinin-neuraminidase protein, and polymerase. The potential role of these amino acid changes in neurotropism, neurovirulence, and neuroattenuation is discussed.

UR - http://www.scopus.com/inward/record.url?scp=0142060847&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0142060847&partnerID=8YFLogxK

U2 - 10.1128/JVI.77.21.11616-11624.2003

DO - 10.1128/JVI.77.21.11616-11624.2003

M3 - Article

C2 - 14557647

AN - SCOPUS:0142060847

VL - 77

SP - 11616

EP - 11624

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 21

ER -