Hydrophobic domains of mouse polyomavirus minor capsid proteins promote membrane association and virus exit from the ER

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F17%3A10337958" target="_blank" >RIV/00216208:11310/17:10337958 - isvavai.cz</a>

Result on the web

<a href="http://onlinelibrary.wiley.com/doi/10.1111/febs.14033/full" target="_blank" >http://onlinelibrary.wiley.com/doi/10.1111/febs.14033/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/febs.14033" target="_blank" >10.1111/febs.14033</a>

Result language

angličtina

Original language name

Hydrophobic domains of mouse polyomavirus minor capsid proteins promote membrane association and virus exit from the ER

Original language description

The minor structural protein VP2 and its shorter variant, VP3, of mouse polyomavirus (MPyV) are essential for virus exit from the endoplasmic reticulum (ER) during viral trafficking to the nucleus. Here, we followed the role of putative hydrophobic domains (HD) of the minor proteins in membrane affinity and viral infectivity. We prepared variants of VP2, each mutated to decrease hydrophobicity of one of three predicted hydrophobic domains: VP2-mHD1, VP2-mHD2 or VP2-mHD3 mutated in HD1 (amino acids (aa) 60-101), HD2 (aa 125-165) or HD3 (aa 287-307), respectively. Transient production of the mutated proteins revealed that only VP2-mHD2 lost the affinity for intracellular membranes. Cytotoxicity connected with the ability of VP2/VP3 to perforate membranes decreased markedly for VP2-mHD2, but only slightly for VP2-mHD1. The mutant VP2-mHD3 exhibited properties similar to the wild-type protein. MPyV genomes, each carrying one of the mutations, were prepared for virus production. MPyV-mHD1 and MPyV-mHD2 viruses could be isolated, while the HD3 mutation in VP2/VP3 prevented virus assembly. We found that both MPyV-mHD1 and MPyV-mHD2 viruses arrived at the ER without delay and were processed by ER residential enzymes. However, the ability to associate with ER membranes was decreased in the case of MPyV-mHD1 and practically abolished in the case of MPyV-mHD2. Interestingly, while MPyV-mHD2 was not infectious, infection of MPyV-mHD1 virus was delayed. These findings reveal that HD2, common to both VP2 and VP3, is responsible for the membrane binding properties of the minor proteins, while HD1 of VP2 is likely required to stabilize VP2-membrane association and to enhance viral exit from the ER.

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

10607 - Virology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

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

Name of the periodical

FEBS Journal

ISSN

1742-464X

e-ISSN

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Volume of the periodical

284

Issue of the periodical within the volume

6

Country of publishing house

GB - UNITED KINGDOM

Number of pages

20

Pages from-to

883-902

UT code for WoS article

000398131500005

EID of the result in the Scopus database

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