A single amino acid change in the C-terminal domain of the matrix protein M1 of influenza B virus confers mouse adaptation and virulence.
Serial passage of an initially avirulent influenza B virus, B/Memphis/12/97, resulted in the selection of a variant which was lethal in mice. Virulence correlated with improved growth in vivo and prolonged replication. Sequencing of the complete coding regions of the parent and mouse-adapted viruses revealed 8 amino acid differences. Sequencing and characterization of intermediate passages suggested that one change in the C-terminal domain of the M1 protein, an asparagine to a serine at position 221, was responsible for acquisition of virulence and lethality. Site-directed mutagenesis of the M segment of a different virus, B/Yamanashi/166/98, to change this amino acid residue confirmed its importance by conferring improved growth and virulence in mice. This observation suggests a role for the C domain of the M1 protein in growth and virulence in a mammalian host.
McCullers
Jonathan A
JA
Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105-2794, USA. jon.mccullrs@stjude.org
Hoffmann
Erich
E
Huber
Victor C
VC
Nickerson
Asia D
AD
D000222:Adaptation, Physiological; D019943:Amino Acid Substitution; D000818:Animals; D001216:Asparagine; D005260:Female; D009981:Influenza B virus / Q000472:pathogenicity* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000821:virology*; D017434:Protein Structure, Tertiary; D012692:Serial Passage; D012694:Serine; D014763:Viral Matrix Proteins / Q000235:genetics / Q000502:physiology*; D014774:Virulence; D014779:Virus Replication
D014763:Viral Matrix Proteins; D012694:Serine; D001216:Asparagine