Expression of the 1918 influenza A virus PB1-F2 enhances the pathogenesis of viral and secondary bacterial pneumonia.
Secondary bacterial pneumonia frequently claimed the lives of victims during the devastating 1918 influenza A virus pandemic. Little is known about the viral factors contributing to the lethality of the 1918 pandemic. Here we show that expression of the viral accessory protein PB1-F2 enhances inflammation during primary viral infection of mice and increases both the frequency and severity of secondary bacterial pneumonia. The priming effect of PB1-F2 on bacterial pneumonia could be recapitulated in mice by intranasal delivery of a synthetic peptide derived from the C-terminal portion of the PB1-F2. Relative to its isogenic parent, an influenza virus engineered to express a PB1-F2 with coding changes matching the 1918 pandemic strain was more virulent in mice, induced more pulmonary immunopathology, and led to more severe secondary bacterial pneumonia. These findings help explain both the unparalleled virulence of the 1918 strain and the high incidence of fatal pneumonia during the pandemic.
McAuley
Julie L
JL
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Hornung
Felicita
F
Boyd
Kelli L
KL
Smith
Amber M
AM
McKeon
Raelene
R
Bennink
Jack
J
Yewdell
Jonathan W
JW
McCullers
Jonathan A
JA
D000818:Animals; D005260:Female; D007249:Inflammation / Q000473:pathology; D053118:Influenza A Virus, H1N1 Subtype / Q000378:metabolism* / Q000472:pathogenicity; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000473:pathology; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis; D011018:Pneumonia, Pneumococcal / Q000209:etiology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D013296:Streptococcus pneumoniae; D014764:Viral Proteins / Q000096:biosynthesis* / Q000138:chemical synthesis / Q000235:genetics; D014774:Virulence
C442816:PB1-F2 protein, Influenza A virus; D010455:Peptides; D011994:Recombinant Proteins; D014764:Viral Proteins