Conserved amino acid markers from past influenza pandemic strains.
BACKGROUND
Finding the amino acid mutations that affect the severity of influenza infections remains an open and challenging problem. Of special interest is better understanding how current circulating influenza strains could evolve into a new pandemic strain. Influenza proteomes from distinct viral phenotype classes were searched for class specific amino acid mutations conserved in past pandemics, using reverse engineered linear classifiers.


RESULTS
Thirty-four amino acid markers associated with host specificity and high mortality rate were found. Some markers had little impact on distinguishing the functional classes by themselves, however in combination with other mutations they improved class prediction. Pairwise combinations of influenza genomes were checked for reassortment and mutation events needed to acquire the pandemic conserved markers. Evolutionary pathways involving H1N1 human and swine strains mixed with avian strains show the potential to acquire the pandemic markers with a double reassortment and one or two amino acid mutations.


CONCLUSIONS
The small mutation combinations found at multiple protein positions associated with viral phenotype indicate that surveillance tools could monitor genetic variation beyond single point mutations to track influenza strains. Finding that certain strain combinations have the potential to acquire pandemic conserved markers through a limited number of reassortment and mutation events illustrates the potential for reassortment and mutation events to lead to new circulating influenza strains.
Allen
Jonathan E
JE
Lawrence Livermore National Laboratory, Livermore, CA, 94551, USA. allen99@llnl.gov
Gardner
Shea N
SN
Vitalis
Elizabeth A
EA
Slezak
Tom R
TR
D000595:Amino Acid Sequence; D000818:Animals; D001717:Birds / Q000821:virology; D017124:Conserved Sequence; D004196:Disease Outbreaks; D019143:Evolution, Molecular; D005819:Genetic Markers; D016679:Genome, Viral; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics*; D005585:Influenza in Birds / Q000453:epidemiology / Q000821:virology; D007251:Influenza, Human / Q000453:epidemiology / Q000821:virology; D009154:Mutation; D040901:Proteomics; D016865:Reassortant Viruses / Q000235:genetics; D016415:Sequence Alignment; D013045:Species Specificity; D013552:Swine; D014764:Viral Proteins / Q000235:genetics
D005819:Genetic Markers; D014764:Viral Proteins