Enhanced susceptibility of Ago1/3 double-null mice to influenza a virus infection

Van Stry, M., Oguin Iii, T. H., Cheloufi, S., Vogel, P., Watanabe, M., Pillai, M. R., Dash, P., Thomas, P. G., Hannon, G. J., Bix, M. (2012) Enhanced susceptibility of Ago1/3 double-null mice to influenza a virus infection. Journal of Virology, 86 (8). pp. 4151-4157. ISSN 0022538X (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/22318144
DOI: 10.1128/jvi.05303-11

Abstract

AbstracrtRNA 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. © 2012, American Society for Microbiology.

Item Type: Paper
Uncontrolled Keywords: argonaute 1 protein argonaute 3 protein argonaute protein unclassified drug animal cell animal experiment animal model animal tissue article controlled study host resistance infection sensitivity influenza A knockout mouse lung alveolitis mouse nonhuman pneumonia priority journal protein function RNA interference virus replication Animals Argonaute Proteins Eukaryotic Initiation Factors Genetic Predisposition to Disease Humans Influenza A virus Lung Mice Mice, 129 Strain Mice, Inbred C57BL Mice, Knockout Orthomyxoviridae Infections
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > AGO
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types
organism description > animal > mammal > rodent > mouse
organism description > virus
CSHL Authors:
Communities: CSHL labs > Hannon lab
CSHL Cancer Center Shared Resources > Animal Services
CSHL Cancer Center Shared Resources > Bioinformatics Service
CSHL Cancer Center Shared Resources > DNA Sequencing Service
CSHL Cancer Center Shared Resources > Flow Cytometry Service
CSHL Cancer Center Shared Resources > Gene Targeting Service
CSHL Cancer Center Shared Resources > Microscopy Service
Depositing User: Matt Covey
Date: 2012
Date Deposited: 09 Jan 2013 15:55
Last Modified: 26 Dec 2014 18:54
PMCID: PMC3318639
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26411

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