The human mucus protease inhibitor and its mutants are novel defensive compounds against infection with influenza A and Sendai viruses

Kido, Hiroshi; Beppu, Yoshihito; Imamura, Yasuhiro; Chen, Ye; Murakami, Meiko; Oba, Kumiko; Towatari, Takae

doi:10.1002/(sici)1097-0282(1999)51:1<79::aid-bip9>3.0.co;2-w

Cited by 29 publications

(17 citation statements)

References 31 publications

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“…The role of oxidative stress has also been studied and investigators report that oxidative stress inhibits GSH [37] which can lead to enhanced virus replication [38]. Oxidative stress can also inhibit mucus antiproteases [39] that regulate the trypsin like serine proteases which cleaves influenza hemagluttinin, effectively enhancing its ability to spread and more readily infect epithelial cells [40,41]. Our study proposes an additional mechanism for this phenomenon.…”

Section: Discussionmentioning

confidence: 75%

Exposure to combustion generated environmentally persistent free radicals enhances severity of influenza virus infection

et al. 2014

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BackgroundExposures to elevated levels of particulate matter (PM) enhance severity of influenza virus infection in infants. The biological mechanism responsible for this phenomenon is unknown. The recent identification of environmentally persistent free radicals (EPFRs) associated with PM from a variety of combustion sources suggests its role in the enhancement of influenza disease severity.MethodsNeonatal mice (< seven days of age) were exposed to DCB230 (combustion derived PM with a chemisorbed EPFR), DCB50 (non-EPFR PM sample), or air for 30 minutes/day for seven consecutive days. Four days post-exposure, neonates were infected with influenza intranasally at 1.25 TCID50/neonate. Neonates were assessed for morbidity (% weight gain, peak pulmonary viral load, and viral clearance) and percent survival. Lungs were isolated and assessed for oxidative stress (8-isoprostanes and glutathione levels), adaptive immune response to influenza, and regulatory T cells (Tregs). The role of the EPFR was also assessed by use of transgenic mice expressing human superoxide dismutase 2.ResultsNeonates exposed to EPFRs had significantly enhanced morbidity and decreased survival following influenza infection. Increased oxidative stress was also observed in EPFR exposed neonates. This correlated with increased pulmonary Tregs and dampened protective T cell responses to influenza infection. Reduction of EPFR-induced oxidative stress attenuated these effects.ConclusionsNeonatal exposure to EPFR containing PM resulted in pulmonary oxidative stress and enhanced influenza disease severity. EPFR-induced oxidative stress resulted in increased presence of Tregs in the lungs and subsequent suppression of adaptive immune response to influenza.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-014-0057-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 75%

Exposure to combustion generated environmentally persistent free radicals enhances severity of influenza virus infection

et al. 2014

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“…The substitution Ile-328→Thr, which is conserved in canine viruses, could have been selected to ensure the required cleavage of precursor HA0 into HA1 and HA2. This could be achieved by optimizing the Gln/Glu-X-Arg− recognition site for a canine protease like tryptase Clara (15) or by increasing the ability of HA0 to compete with mucus protease inhibitors known to be present in the respiratory tract (16).…”

Section: Significancementioning

confidence: 99%

Recent evolution of equine influenza and the origin of canine influenza

Collins¹,

Vachieri²,

Haire³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Equine influenza viruses of the H3N8 subtype have caused outbreaks of respiratory disease in horses throughout the world since their discovery in 1963 in Florida. In 2004 an equine virus in circulation was transmitted to dogs and subsequently spread throughout the United States and to Europe. Comparative analyses of the structures of hemagglutinin glycoproteins of equine and canine viruses by X-ray crystallography locate the sites of variation on the molecules, indicate a role in determining binding specificity for an amino acid sequence difference in the receptor binding site, and describe a unique structural difference in the membrane fusion region in recent equine and canine virus HAs by comparison with all other known HAs. These differences are proposed to have facilitated cross-species transfer.

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“…The induction of influenza virus infectivity by host cell proteases is strictly regulated by inhibitors of the serine proteases such as human mucus protease inhibitor (MPI) in the upper respiratory tract (Kido et al, 1999) and pulmonary surfactant (Kido et al, 1993) in the lower respiratory tract. MPI accounts for 70-90% of the protease-inhibitory capacity of normal bronchial secretions.…”

Section: Discussionmentioning

confidence: 99%

Effect of a Plant Polyphenol-Rich Extract on the Lung Protease Activities of Influenza-Virus-Infected Mice

Serkedjieva

Toshkova

Antonova-Nikolova

et al. 2007

Antivir Chem Chemother

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Influenza infection was induced in white mice by intranasal inoculation of the virus A/Aichi/2/68 (H3N2). The lung protease and the proteaseinhibitory activities were followed for 9 days after infection. The intranasal application of a polyphenol-rich extract (PC) isolated from Geranium sanguineum L. induced a continuous rise in the anti-protease activity but did not cause substantial changes in the lung protease activity of healthy mice. Influenza virus infection triggered a slight reduction in protease activity in the lungs at 5 and 48 h post infection (p.i.) and a marked increase at 24 h and 6 day p.i.. Protease inhibition in the lungs was reduced at 24 and 48 h p.i. and an increase was observed at 5 h and 6 and 9 days p.i.. PC treatment brought both activities to normal levels. The restoration of the examined parameters was consistent with a prolongation of mean survival time and reduction of mortality rate, infectious virus titre and lung consolidation. PC reinstated superoxide production by alveolar macrophages and increased their number in virus-infected mice. The favourable effect on the protease and the protease-inhibitory activities in the lungs of influenza-virus-infected mice apparently contributes to the overall protective effect of PC in the murine experimental influenza A/Aichi infection. The antiviral effect of the individual constituents was evaluated.

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The human mucus protease inhibitor and its mutants are novel defensive compounds against infection with influenza A and Sendai viruses

Cited by 29 publications

References 31 publications

Exposure to combustion generated environmentally persistent free radicals enhances severity of influenza virus infection

Exposure to combustion generated environmentally persistent free radicals enhances severity of influenza virus infection

Recent evolution of equine influenza and the origin of canine influenza

Effect of a Plant Polyphenol-Rich Extract on the Lung Protease Activities of Influenza-Virus-Infected Mice

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