tetano
Editor, Senior Moderator
J Virol. 2012 Aug 22. [Epub ahead of print]
Intranasal treatment with poly I:C protects aged mice from lethal respiratory viral infections.
Zhao J, Wohlford-Lenane C, Zhao J, Fleming E, Lane TE, McCray PB Jr, Perlman S.
Source
Departments of Microbiology.
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 of 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 pre-treatment of aged mice with poly I:C (TLR3 agonist), and to a lesser extent, CpG, R848 or LPS (TLR9, TLR7/8 or TLR4 agonists), provided a high level of protection (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 pre-treatment upregulated IFN-β, IFN-γ, IL-1β and TNF gene expression in the lungs. Intranasal pre-treatment with IFN-β or IFN-γ but not IL-1β or TNF also protected aged mice, consistent with the notion that poly I:C pre-treatment, 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.
PMID:
22915814
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22915814
Intranasal treatment with poly I:C protects aged mice from lethal respiratory viral infections.
Zhao J, Wohlford-Lenane C, Zhao J, Fleming E, Lane TE, McCray PB Jr, Perlman S.
Source
Departments of Microbiology.
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 of 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 pre-treatment of aged mice with poly I:C (TLR3 agonist), and to a lesser extent, CpG, R848 or LPS (TLR9, TLR7/8 or TLR4 agonists), provided a high level of protection (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 pre-treatment upregulated IFN-β, IFN-γ, IL-1β and TNF gene expression in the lungs. Intranasal pre-treatment with IFN-β or IFN-γ but not IL-1β or TNF also protected aged mice, consistent with the notion that poly I:C pre-treatment, 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.
PMID:
22915814
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22915814