Inhibition of placental trophoblast fusion by guanylate-binding protein 5
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F25%3A00645075" target="_blank" >RIV/68378050:_____/25:00645075 - isvavai.cz</a>
Result on the web
<a href="https://www.science.org/doi/epdf/10.1126/sciadv.adt5388" target="_blank" >https://www.science.org/doi/epdf/10.1126/sciadv.adt5388</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1126/sciadv.adt5388" target="_blank" >10.1126/sciadv.adt5388</a>
Alternative languages
Result language
angličtina
Original language name
Inhibition of placental trophoblast fusion by guanylate-binding protein 5
Original language description
Syncytin-1 and Syncytin-2 are envelope glycoproteins encoded by human endogenous retroviruses that have been exapted for the fusion of cytotrophoblast cells into syncytiotrophoblasts during placental development. Pregnancy complications like preeclampsia are associated with altered expression of interferon-stimulated genes, including guanylate-binding protein 5 (GBP5). Here, we show that misdirected antiviral activity of GBP5 impairs processing and activation of Syncytin-1. In contrast, the proteolytic activation of Syncytin-2 is not affected by GBP5, and its fusogenic activity is only modestly reduced. Mechanistic analyses revealed that Syncytin-1 is mainly cleaved by the GBP5 target furin, whereas Syncytin-2 is also efficiently processed by the proprotein convertase subtilisin/kexin type 7 (PCSK7) and thus resistant to GBP5-mediated restriction. Mutational analyses mapped PCSK7 processing of Syncytin-2 to a leucine residue upstream of the polybasic cleavage site. In summary, we identified an innate immune mechanism that impairs the activity of a co-opted endogenous retroviral envelope protein during pregnancy and may potentially contribute to the pathogenesis of pregnancy disorders.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/LX22NPO5103" target="_blank" >LX22NPO5103: National Institute of Virology and Bacteriology</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Science Advances
ISSN
2375-2548
e-ISSN
2375-2548
Volume of the periodical
11
Issue of the periodical within the volume
19
Country of publishing house
US - UNITED STATES
Number of pages
14
Pages from-to
eadt5388
UT code for WoS article
001483895900010
EID of the result in the Scopus database
2-s2.0-105004779558