Intranasal treatment with poly(I•C) protects aged mice from lethal respiratory virus infections

Jincun Zhao; Christine Wohlford-Lenane; Jingxian Zhao; Erica Fleming; Thomas E Lane; Paul B McCray Jr; Stanley Perlman

doi:10.1128/JVI.01410-12

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Intranasal treatment with poly(I•C) protects aged mice from lethal respiratory virus infections

Journal article

Open access

Peer reviewed

Intranasal treatment with poly(I•C) protects aged mice from lethal respiratory virus infections

Jincun Zhao, Christine Wohlford-Lenane, Jingxian Zhao, Erica Fleming, Thomas E Lane, Paul B McCray Jr and Stanley Perlman

Journal of virology, Vol.86(21), pp.11416-11424

11/2012

DOI: 10.1128/JVI.01410-12

PMCID: PMC3486278

PMID: 22915814

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Abstract

In the 2002-2003 severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic, no patients under 24 years of age died, while mortality was greater than 50% in those over 65 years. Greater than 90% of all deaths from influenza A virus (IAV) occur in the elderly (>65 years of age). To address this age-related susceptibility to SARS-CoV and IAV, we infected C57BL/6 (B6) mice with mouse-adapted SARS-CoV (MA15) or IAV (PR8), both of which cause severe disease in aged mice. Intranasal pretreatment of aged mice with poly(I·C) (a TLR3 agonist) and, to a lesser extent, CpG, R848, or lipopolysaccharide (TLR9, TLR7/8, or TLR4 agonists), provided a high level of protection [90% to 100% survival rate after poly(I·C) treatment] against lethal MA15 or IAV challenge and reduced pathological changes and virus loads in the lungs at early times after infection. Poly(I·C) pretreatment upregulated beta interferon (IFN-β), IFN-γ, IL-1β, and tumor necrosis factor (TNF) gene expression in the lungs. Intranasal pretreatment with IFN-β or IFN-γ but not IL-1β or TNF also protected aged mice, consistent with the notion that poly(I·C) pretreatment functioned, at least in part, by inducing IFN-β and IFN-γ. We also identified a potential cellular target for poly(I·C) by showing that treatment inhibited virus replication in primary human airway epithelial cells. These results suggest that intranasal poly(I·C) should be evaluated as a prophylactic agent in aged individuals at high risk for contracting SARS-CoV or IAV infections.

Orthomyxoviridae Infections - prevention & control

Lung - pathology

Oligodeoxyribonucleotides - administration & dosage

Adjuvants, Immunologic - administration & dosage

Poly I-C - administration & dosage

Lipopolysaccharides - administration & dosage

Mice, Inbred C57BL

Cytokines - secretion

Severe Acute Respiratory Syndrome - mortality

Administration, Intranasal

SARS Virus - pathogenicity

Viral Load

Lung - virology

Severe Acute Respiratory Syndrome - prevention & control

Animals

Orthomyxoviridae Infections - mortality

Survival Analysis

Influenza A virus - pathogenicity

Mice

Disease Models, Animal

Details

Title: Subtitle: Intranasal treatment with poly(I•C) protects aged mice from lethal respiratory virus infections
Creators: Jincun Zhao - Departments of Microbiology, University of Iowa, Iowa City, Iowa, USA. jincun-zhao@uiowa.edu
Christine Wohlford-Lenane
Jingxian Zhao
Erica Fleming
Thomas E Lane
Paul B McCray Jr
Stanley Perlman
Resource Type: Journal article
Publication Details: Journal of virology, Vol.86(21), pp.11416-11424
DOI: 10.1128/JVI.01410-12
PMID: 22915814
PMCID: PMC3486278
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: United States
Grant note: R01 NS041249 / NINDS NIH HHS R01AI091322 / NIAID NIH HHS R01 AI091322 / NIAID NIH HHS P01 AI060699 / NIAID NIH HHS P0106099 / PHS HHS
Language: English
Date published: 11/2012
Academic Unit: Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777476002771

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