Scopus
🔓 Açık Erişim YÖKSİS Eşleşti
Human TMEFF1 is a restriction factor for herpes simplex virus in the brain
Nature · Ağustos 2024
YÖKSİS Kayıtları
Human TMEFF1 is a restriction factor for herpes simplex virus in the brain
Nature · 2024 SCI-Expanded
DOÇENT MELİKE EMİROĞLU →
Makale Bilgileri
DergiNature
Yayın TarihiAğustos 2024
Cilt / Sayfa632 · 390-400
Scopus ID2-s2.0-85199348297
Erişim🔓 Açık Erişim
Özet
Most cases of herpes simplex virus 1 (HSV-1) encephalitis (HSE) remain unexplained1,2. Here, we report on two unrelated people who had HSE as children and are homozygous for rare deleterious variants of TMEFF1, which encodes a cell membrane protein that is preferentially expressed by brain cortical neurons. TMEFF1 interacts with the cell-surface HSV-1 receptor NECTIN-1, impairing HSV-1 glycoprotein D- and NECTIN-1-mediated fusion of the virus and the cell membrane, blocking viral entry. Genetic TMEFF1 deficiency allows HSV-1 to rapidly enter cortical neurons that are either patient specific or derived from CRISPR–Cas9-engineered human pluripotent stem cells, thereby enhancing HSV-1 translocation to the nucleus and subsequent replication. This cellular phenotype can be rescued by pretreatment with type I interferon (IFN) or the expression of exogenous wild-type TMEFF1. Moreover, ectopic expression of full-length TMEFF1 or its amino-terminal extracellular domain, but not its carboxy-terminal intracellular domain, impairs HSV-1 entry into NECTIN-1-expressing cells other than neurons, increasing their resistance to HSV-1 infection. Human TMEFF1 is therefore a host restriction factor for HSV-1 entry into cortical neurons. Its constitutively high abundance in cortical neurons protects these cells from HSV-1 infection, whereas inherited TMEFF1 deficiency renders them susceptible to this virus and can therefore underlie HSE.
Yazarlar (49)
1
Yi Hao Chan
ORCID: 0000-0003-0329-238X
2
Zhiyong Liu
ORCID: 0000-0001-6473-348X
3
Paul Bastard
4
Noopur Khobrekar
5
Kennen M. Hutchison
6
Yasuhiro Yamazaki
7
Qing Fan
8
Daniela Matuozzo
9
Oliver Harschnitz
ORCID: 0000-0001-6496-881X
10
Nacim Kerrouche
11
Koji Nakajima
12
Param Amin
13
Ahmad Yatim
14
Darawan Rinchai
15
Jie Chen
16
Peng Zhang
17
Gabriele Ciceri
ORCID: 0000-0002-8481-9771
18
Jia Chen
19
Kerry Dobbs
ORCID: 0000-0002-3432-3137
20
Serkan Belkaya
21
Danyel Lee
ORCID: 0000-0003-3124-0245
22
Adrian Gervais
23
Kürşad Aydin
24
Ayşe Kartal
25
Mary L. Hasek
26
Shuxiang Zhao
27
Eduardo Garcia Reino
ORCID: 0000-0002-4781-3864
28
Yoon Seung Lee
ORCID: 0000-0002-9988-8905
29
Yoann Seeleuthner
ORCID: 0000-0002-1878-8567
30
Matthieu Chaldebas
31
Rasheed Bailey
32
Catherine Vanhulle
33
Lazaro Lorenzo
34
Soraya Boucherit
ORCID: 0000-0002-8819-7594
35
Flore Rozenberg
36
Nico Marr
37
Trine H. Mogensen
38
Mélodie Aubart
39
Aurélie Cobat
ORCID: 0000-0001-7209-6257
40
Olivier Dulac
41
Melike Emiroglu
ORCID: 0000-0003-1307-0246
42
Søren R. Paludan
ORCID: 0000-0001-9180-4060
43
Laurent Abel
ORCID: 0000-0001-7016-6493
44
Luigi Notarangelo
ORCID: 0000-0002-8335-0262
45
Richard Longnecker
ORCID: 0000-0001-7175-6217
46
Greg Smith
ORCID: 0000-0001-9644-8472
47
Lorenz Studer
ORCID: 0000-0003-0741-7987
48
Jean Laurent Casanova
ORCID: 0000-0002-7782-4169
49
Shen Ying Zhang
ORCID: 0000-0002-9449-3672
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Aarhus Universitet
Aarhus Denmark
Aarhus Universitetshospital
Aarhus Denmark
Bilkent Üniversitesi
Ankara Turkey
CHU Rouen Normandie
Rouen France
Fondazione Human Technopole
Milan Italy
Hopital Cochin AP-HP
Paris France
Hôpital Necker Enfants Malades
Paris France
Howard Hughes Medical Institute
Chevy Chase United States
İstanbul Medipol Üniversitesi
Istanbul Turkey
Memorial Sloan-Kettering Cancer Center
New York United States
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda United States
Northwestern University Feinberg School of Medicine
Chicago United States
Paris Cité University
Paris France
Rockefeller University
New York United States
Sahlgrenska Akademin
Gothenburg Sweden
Selçuk Tip Fakültesi
Konya Turkey
Selçuk Üniversitesi
Selçuklu Turkey
Sidra Medicine
Doha Qatar
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49
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