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RIP3 deficiency ameliorates inflammatory response in mice infected with influenza H7N9 virus infection.

ABSTRACT: Influenza H7N9 virus infection causes an acute, highly contagious respiratory illness that triggers cell death of infected cells and airway epithelial destruction. RIP3 is a key regulator of cell death responses to a growing number of viral and microbial agents. This study aimed to investigate the role of RIP3 in inflammation of influenza H7N9 virus infection. Here, RIP3 knock out (RIP3-/-) mice and littermate wild type mice were infected intranasally with influenza H7N9 virus (A/Fujian/S03/2015) to determine the contribution of RIP3 to the inflammatory response of influenza H7N9 virus infection. It was found that RIP3-/- mice infected with H7N9 virus showed higher survival and less weight loss, compared with wild type littermate mice. In addition, RIP3-/- mice had fewer regions of edema, infiltration with inflammatory cells, and alvelolar collapses, and the secretions of IL-1?, IL-6, RANTES and MIP-1 in BALF were significantly decreased on days 3 and 7 p.i. when compared with WT mice. Moreover, caspase 1/IL1? signaling was found to be invovled in RIP3 associated imflammation of influenza H7N9 virus, but not RIP3/MLKL dependent necrosis. In the conclusion, our results indicated that RIP3 deficiency can protect mice from the infection of influenza H7N9 virus by downregulating caspase 1/IL1? signaling, which provided edivence of the RIP3 invovled necroptosis independent manner.

SUBMITTER: Xu YL

PROVIDER: S-EPMC5438603 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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RIP3 deficiency ameliorates inflammatory response in mice infected with influenza H7N9 virus infection.

Xu Yu-Lin YL Tang Hai-Lin HL Peng Hao-Ran HR Zhao Ping P Qi Zhong-Tian ZT Wang Wen W

Oncotarget 20170401 17

Influenza H7N9 virus infection causes an acute, highly contagious respiratory illness that triggers cell death of infected cells and airway epithelial destruction. RIP3 is a key regulator of cell death responses to a growing number of viral and microbial agents. This study aimed to investigate the role of RIP3 in inflammation of influenza H7N9 virus infection. Here, RIP3 knock out (RIP3-/-) mice and littermate wild type mice were infected intranasally with influenza H7N9 virus (A/Fujian/S03/2015 ...[more]

PMID: 28423682

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Project description:UnlabelledA novel avian-origin influenza A/H7N9 virus infecting humans was first identified in March 2013 and, as of 30 May 2013, has caused 132 human infections leading to 33 deaths. Phylogenetic studies suggest that this virus is a reassortant, with the surface hemagglutinin (HA) and neuraminidase (NA) genes being derived from duck and wild-bird viruses, respectively, while the six "internal gene segments" were derived from poultry H9N2 viruses. Here we determine the pathogenicity of a human A/Shanghai/2/2013 (Sh2/H7N9) virus in healthy adult mice in comparison with that of A/chicken/Hong Kong/HH8/2010 (ck/H9N2) virus, highly pathogenic avian influenza (HPAI) A/Hong Kong/483/1997 (483/H5N1) virus, and a duck influenza A H7N9 virus of different genetic derivation, A/duck/Jiangxi/3286/2009 (dk/H7N9). Intranasal infection of mice with Sh2/H7N9 virus doses of 10(3), 10(4), and 10(5) PFU led to significant weight loss without fatality. This virus was more pathogenic than dk/H7N9 and ck/H9N2 virus, which has six internal gene segments that are genetically similar to Sh2/H7N9. Sh2/H7N9 replicated well in the nasal cavity and lung, but there was no evidence of virus dissemination beyond the respiratory tract. Mice infected with Sh2/H7N9 produced higher levels of proinflammatory cytokines in the lung and serum than did ck/H9N2 and dk/H7N9 but lower levels than 483/H5N1. Cytokine induction was positively correlated with virus load in the lung at early stages of infection. Our results suggest that Sh2/H7N9 virus is able to replicate and cause disease in mice without prior adaptation but is less pathogenic than 483/H5N1 virus.ImportanceAn H7N9 virus isolate causing fatal human disease was found to be more pathogenic for mice than other avian H9N2 or H7N9 viruses but less pathogenic than the highly pathogenic avian influenza virus (HPAI) H5N1. Similarly, the ability of Sh2/H7N9 to elicit proinflammatory cytokines in the lung and serum of mice was intermediate to ck/H9N2 and dk/H7N9 on the one hand and HPAI H5N1 on the other. These findings accord with the observed epidemiology in humans, in whom, as with seasonal influenza viruses, H7N9 viruses cause severe disease predominantly in older persons while HPAI H5N1 can cause severe respiratory disease and death in children and young adults.

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RIP3 deficiency ameliorates inflammatory response in mice infected with influenza H7N9 virus infection.

Publications

RIP3 deficiency ameliorates inflammatory response in mice infected with influenza H7N9 virus infection.

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