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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Biological Chemistry

ISSN

1431-6730

e-ISSN

—

Svazek periodika

399

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

12

Strana od-do

1053-1064

Kód UT WoS článku

000441526200012

EID výsledku v databázi Scopus

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