Kallikrein-related peptidase 5 and seasonal influenza viruses, limitations of the experimental models for activating proteases

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F18%3A00494243" target="_blank" >RIV/68378050:_____/18:00494243 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1515/hsz-2017-0340" target="_blank" >http://dx.doi.org/10.1515/hsz-2017-0340</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1515/hsz-2017-0340" target="_blank" >10.1515/hsz-2017-0340</a>

Result language

angličtina

Original language name

Kallikrein-related peptidase 5 and seasonal influenza viruses, limitations of the experimental models for activating proteases

Original language description

Every year, influenza A virus (IAV) affects and kills many people worldwide. The viral hemagglutinin (HA) is a critical actor in influenza virus infectivity which needs to be cleaved by host serine proteases to exert its activity. KLK5 has been identified as an activating protease in humans with a preference for the H3N2 IAV subtype. We investigated the origin of this preference using influenza A/Puerto Rico/8/34 (PR8, H1N1) and A/Scotland/20/74 (Scotland, H3N2) viruses. Pretreatment of noninfectious virions with human KLK5 increased infectivity of Scotland IAV in MDCK cells and triggered influenza pneumonia in mice. These effects were not observed with the PR8 IAV. Molecular modeling and in vitro enzymatic studies of peptide substrates and recombinant HAs revealed that the sequences around the cleavage site do not represent the sole determinant of the KLK5 preference for the H3N2 subtype. Using mouse Klk5 and Klk5-deficient mice, we demonstrated in vitro and in vivo that the mouse ortholog protease is not an IAV activating enzyme. This may be explained by unfavorable interactions between H3HA and mKlk5. Our data highlight the limitations of some approaches used to identify IAV-activating proteases.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Biological Chemistry

ISSN

1431-6730

e-ISSN

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Volume of the periodical

399

Issue of the periodical within the volume

9

Country of publishing house

DE - GERMANY

Number of pages

12

Pages from-to

1053-1064

UT code for WoS article

000441526200012

EID of the result in the Scopus database

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