The role of IFITM proteins in tick-borne encephalitis virus infection

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F22%3A00078862" target="_blank" >RIV/00209805:_____/22:00078862 - isvavai.cz</a>

Result on the web

<a href="https://pubmed.ncbi.nlm.nih.gov/34613785/" target="_blank" >https://pubmed.ncbi.nlm.nih.gov/34613785/</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1128/JVI.01130-21" target="_blank" >10.1128/JVI.01130-21</a>

Result language

angličtina

Original language name

The role of IFITM proteins in tick-borne encephalitis virus infection

Original language description

Tick-borne encephalitis virus (TBEV), of the genus Flavivirus, is a causative agent of severe encephalitis in endemic regions of northern Asia and central and northern Europe. Interferon induced transmembrane proteins (IFITMs) are restriction factors that inhibit the replication cycles of numerous viruses, including flaviviruses such as the West Nile virus, dengue virus, and Zika virus. Here, we demonstrate the role of IFITM1, IFITM2, and IFITM3 in the inhibition of TBEV infection and in protection against virus-induced cell death. We show the most significant role being that of IFITM3, including the dissection of its functional motifs by mutagenesis. Furthermore, through the use of CRISPR-Cas9-generated IFITM1/3-knockout monoclonal cell lines, we confirm the role and additive action of endogenous IFITMs in TBEV suppression. However, the results of co-culture assays suggest that TBEV might partially escape IFN- and IFITM-mediated suppression during high-density co-culture infection when the virus enters naïve cells directly from infected donor cells. Thus, cell-to-cell spread may constitute a strategy for virus escape from innate host defenses. Importance: TBEV infection may result in encephalitis, chronic illness or death. TBEV is endemic in northern Asia and Europe; however, due to climate change, new endemic centers arise. Although effective TBEV vaccines have been approved, vaccination coverage is low, and, due to the lack of specific therapeutics, infected individuals depend on their immune responses to control the infection. The IFITM proteins are components of the innate antiviral defenses that suppress cell entry of many viral pathogens. However, no studies regarding the role of IFITM proteins in the TBEV infection have been published so far. Understanding of antiviral innate immune responses is crucial for future development of antiviral strategies. Here, we show the important role of IFITM proteins in the inhibition of TBEV infection and virus-mediated cell death. However, our data suggest that TBEV cell-to-cell spread may be less prone to both IFN- and IFITM-mediated suppression, potentially facilitating escape from IFITM-mediated immunity.

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

—

OECD FORD branch

10608 - Biochemistry and molecular biology

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

2022

Confidentiality

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

Name of the periodical

Journal of virology

ISSN

0022-538X

e-ISSN

1098-5514

Volume of the periodical

96

Issue of the periodical within the volume

1

Country of publishing house

US - UNITED STATES

Number of pages

16

Pages from-to

"e01130"-21

UT code for WoS article

000766757400009

EID of the result in the Scopus database

2-s2.0-85123069016