Amino acid changes in the hemagglutinin and matrix proteins of influenza a (H2) viruses adapted to mice.
Mouse-adapted (MA) variants of human and avian influenza A (H2) viruses were generated and characterized with respect to acquisition of virulence in mice. From the nucleotide sequence the amino acid sequence was deduced. The HA1 subunit of the hemagglutinin (HA) contained three amino acid substitutions in the A/black duck/New Jersey/1580/78-MA variant (Glu216-->Asp, Lys307-->Arg, and Thr318-->Ile) and two substitutions in the A/JapanxBellamy/57-MA variant (Lys25-->Thr and Ser203-->Phe). In the M1 protein, there were two substitutions in the A/black duck/New Jersey/1580/78-MA variant (Asn30-->Asp and Gln214-->His) and a single substitution in the A/JapanxBellamy/57-MA variant (Met179-->Lys). The M2 protein amino acid sequences of the parental virus and the MA variants differed by a single identical mutation (Asn93-->Ser). The localization and atomic distances of the observed mutations on the three-dimensional (3D) structure of the HA protein were analyzed for influenza H2 viruses. The obtained results were similar to those published earlier on H1, H3 and H5 subtypes. The amino acid changes in the HA protein could be divided into two groups. In one group the substitutions were situated at the top of the molecule, while in the other group they were clustered in the stem area at the interface region between three HA monomers. The analysis revealed that the substitutions observed in the MA variants probably increase the flexibility of the HA molecule and/or weaken the interactions between monomers or subunits in the HA trimer. The relationships of the observed amino acid changes in the HA and M proteins to the biological properties of the respective viruses and possible mechanisms involved in the acquisition of viral virulence are discussed.
The D.I. Ivanovsky Institute of Virology, Russian Academy of Medical Sciences, Moscov.
E A
EA
Govorkova
A S
AS
Gambaryan
E C
EC
Claas
Y A
YA
Smirnov
D019943:Amino Acid Substitution; D000818:Animals; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D001717:Birds; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics; D002460:Cell Line; D002642:Chick Embryo; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D009980:Influenza A virus / Q000235:genetics* / Q000472:pathogenicity; D008168:Lung / Q000821:virology; D051379:Mice; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics*; D000086082:Viroporin Proteins
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014763:Viral Matrix Proteins; C031540:M-protein, influenza virus; C488936:M1 protein, Influenza A virus; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C014689:streptococcal M protein