FUNCTIONAL RECONSTRUCTION OF SYNCYTIN‑2 ENVELOPEGLYCOPROTEIN

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F23%3A00580714" target="_blank" >RIV/68378050:_____/23:00580714 - isvavai.cz</a>

Výsledek na webu

<a href="http://ccsss.cz/index.php/ccsss/issue/view/41" target="_blank" >http://ccsss.cz/index.php/ccsss/issue/view/41</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

FUNCTIONAL RECONSTRUCTION OF SYNCYTIN‑2 ENVELOPEGLYCOPROTEIN

Popis výsledku v původním jazyce

Syncytin-2 is a membrane protein expressed in the human placenta1. After interaction with its partner, MFSD2a, Syncytin‑2 facilitates membrane fusion of cytotrophoblast cells into a multinucleated syncytiotrophoblast2. This layer acts as a fetomaternal barrier, facilitating the selective transport of nutrients and metabolites and protecting the fetus against the mother’s immune system. The fusogenic function of Syncytin‑2 relates to its origin. A retrovirus enveloped with Syncytin-2 infected a human ancestor 40 million years ago and integrated into its DNA as HERV-FRD1. Since then, Syncytin‑2 has kept its ability to recognize MFSD2a receptor and mediate membrane fusion. However, it has lost the ability to envelop an infectious virus.We aim to identify and revert the mutations in Syncytin-2 that restrict the original envelope function. Namely, we address its expression at the level of splicing and signal peptide recognition, and we are especially interested in its cytoplasmic tail, which probably modulates the fusogenic activity and blocks its incorporation into budding virions. Modifications of these regulatory regions may help release infectious viral particles.Such an infectious virus in non-replicative settings will be exploited in future research of MFSD2a-Syncytin-2 interactions and mechanisms of antiviral innate immune response. Moreover, we would like to investigate the molecular link between human diseases and Syncytin-2 function.

Název v anglickém jazyce

FUNCTIONAL RECONSTRUCTION OF SYNCYTIN‑2 ENVELOPEGLYCOPROTEIN

Popis výsledku anglicky

Syncytin-2 is a membrane protein expressed in the human placenta1. After interaction with its partner, MFSD2a, Syncytin‑2 facilitates membrane fusion of cytotrophoblast cells into a multinucleated syncytiotrophoblast2. This layer acts as a fetomaternal barrier, facilitating the selective transport of nutrients and metabolites and protecting the fetus against the mother’s immune system. The fusogenic function of Syncytin‑2 relates to its origin. A retrovirus enveloped with Syncytin-2 infected a human ancestor 40 million years ago and integrated into its DNA as HERV-FRD1. Since then, Syncytin‑2 has kept its ability to recognize MFSD2a receptor and mediate membrane fusion. However, it has lost the ability to envelop an infectious virus.We aim to identify and revert the mutations in Syncytin-2 that restrict the original envelope function. Namely, we address its expression at the level of splicing and signal peptide recognition, and we are especially interested in its cytoplasmic tail, which probably modulates the fusogenic activity and blocks its incorporation into budding virions. Modifications of these regulatory regions may help release infectious viral particles.Such an infectious virus in non-replicative settings will be exploited in future research of MFSD2a-Syncytin-2 interactions and mechanisms of antiviral innate immune response. Moreover, we would like to investigate the molecular link between human diseases and Syncytin-2 function.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/LX22NPO5103" target="_blank" >LX22NPO5103: Národní institut virologie a bakteriologie</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

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