Pathogenicity of different PR8 influenza A virus variants in mice is determined by both viral and host factors.
Experimental mouse models were used to compare virulence and reproduction rate of three mouse-adapted variants of the PR8 influenza A virus strain. We observed large differences in pathogenicity in two mouse strains. The PR8M variant was lethal in DBA/2J mice but not in C57BL/6J mice, whereas PR8F and hvPR8 variants were lethal in both mouse strains. High lethality of PR8M in DBA/2J correlated with high viral load at early time points after infection and spread of the virus into alveolar regions. Also, higher viral loads and mortality in mice infected with PR8F resulted in a higher number of infiltrating leukocytes. 3D-protein structure predictions of the HA indicated amino acid sequence alterations which may render the HA cleavage site in PR8F more accessible to host proteases. Infection of C57BL/6J mice with a re-assorted PR8 virus revealed that the HA gene is the main determinant of virulence of the PR8F variant.
Department of Infection Genetics, Helmholtz Centre for Infection Research and University of Veterinary Medicine Hannover, Braunschweig, Germany.
Paulina
P
Blazejewska
Lukasz
L
Koscinski
Nuno
N
Viegas
Darisuren
D
Anhlan
Stephan
S
Ludwig
Klaus
K
Schughart
D000818:Animals; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity*; D007962:Leukocytes / Q000276:immunology; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008958:Models, Molecular; D009976:Orthomyxoviridae Infections / Q000401:mortality / Q000473:pathology* / Q000821:virology*; D017434:Protein Structure, Tertiary; D016019:Survival Analysis; D019562:Viral Load; D014774:Virulence; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D037521:Virulence Factors