Enhanced susceptibility of Ago1/3 double-null mice to influenza A virus infection.
RNA interference (RNAi) is a critical component of many cellular antiviral responses in plants, invertebrates, and mammals. However, its in vivo role in host protection from the negative-sense RNA virus influenza virus type A (flu) is unclear. Here we have examined the role of RNAi in host defense to flu by analyzing Argonaute 1 and 3 double-knockout mice deficient in components of the RNA-induced silencing complex. Compared to littermate controls, flu-infected double-knockout mice exhibited increased mortality, consistent with more severe alveolitis and pneumonitis. These data indicate that optimal resistance to flu requires Argonaute 1 and/or 3. Enhanced mortality of double-knockout mice was not associated either with increased viral replication or with differential pulmonary recruitment or function of innate and adaptive immune cells. Given the absence of detectable immune defects, our results support the notion that the enhanced flu susceptibility of double-knockout mice arises from an intrinsic impairment in the ability of lung cells to tolerate flu-elicited inflammation.
Department of Immunology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA.
Melanie
M
Van Stry
Thomas H
TH
Oguin
Sihem
S
Cheloufi
Peter
P
Vogel
Makiko
M
Watanabe
Meenu R
MR
Pillai
Pradyot
P
Dash
Paul G
PG
Thomas
Gregory J
GJ
Hannon
Mark
M
Bix
D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics*; D039642:Eukaryotic Initiation Factors / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000235:genetics* / Q000276:immunology; D034622:RNA Interference; D014779:Virus Replication
C549050:Ago1 protein, mouse; C572771:Ago3 protein, mouse; D060565:Argonaute Proteins; D039642:Eukaryotic Initiation Factors