The Hippo Terminal Effector Yap Boosts Enterovirus Replication in Type 1 Diabetes

The Hippo Terminal Effector Yap Boosts Enterovirus Replication in Type 1 Diabetes Publisher Pubmed

Geravandi S ; Liu H ; Pahwa H ; Madduri MK ; Atawneh F ; Miraki Feriz A ; Rafizadeh S ; Kruf AE ; Khazaei M ; Bahrami P ; Gotti D ; Elawour M ; Elgamal RM ; Grasso AM Show All Authors

Geravandi S
Liu H
Pahwa H
Madduri MK
Atawneh F
Miraki Feriz A
Rafizadeh S
Kruf AE
Khazaei M
Bahrami P
Gotti D
Elawour M
Elgamal RM
Grasso AM
Bund D
Lupse B
Azizi Z
Zabad O
Bouzakri K
Horwitz M
Pugliese A
Maedler K
Ardestani A

Source: Nature Communications Published:2025

Abstract

Type 1 diabetes (T1D) risk has been associated with enteroviral infections, particularly coxsackieviruses B (CVB). Cellular host factors contributing to virus-induced islet autoimmunity remain unclear. We show that the Hippo pathway effector Yes-associated Protein (YAP) is markedly upregulated in the exocrine and endocrine pancreas of T1D and at-risk autoantibody-positive (AAb+) donors, along with its target CTGF. YAP expression correlates with CVB RNA presence, often in or near infected cells. YAP overexpression enhances CVB replication, islet inflammation, and β-cell apoptosis, whereas its inhibition halts viral replication in primary and immortalized pancreatic cells. In exocrine-islet co-cultures, CVB triggers YAP and target gene expression. In mice, chronic β-cell YAP expression impairs glucose tolerance, abolishes insulin secretion, and promotes β-cell dedifferentiation. Mechanistically, YAP, in complex with its transcription factor TEAD, induces its own negative regulator MST1. MST1 inhibition boosts viral replication and reduces β-cell apoptosis, constituting a negative feedback loop in which the reciprocal antagonism between YAP and MST1 balances viral replication and β-cell death during CVB infections. YAP is thus an important host factor for enteroviral amplification, offering a potential antiviral target in T1D. © 2025 Elsevier B.V., All rights reserved.

Style	Citing Format
MLA	Geravandi S, et al.. "The Hippo Terminal Effector Yap Boosts Enterovirus Replication in Type 1 Diabetes." Nature Communications, vol. 16, no. 1, 2025, pp. -.
APA	Geravandi S, Liu H, Pahwa H, Madduri MK, Atawneh F, Miraki Feriz A, Rafizadeh S, Kruf AE, Khazaei M, Bahrami P, Gotti D, Elawour M, Elgamal RM, Grasso AM, Bund D, Lupse B, Azizi Z, Zabad O, Bouzakri K, ... Ardestani A (2025). The Hippo Terminal Effector Yap Boosts Enterovirus Replication in Type 1 Diabetes. Nature Communications, 16(1), -.
Chicago	Geravandi S, Liu H, Pahwa H, Madduri MK, Atawneh F, Miraki Feriz A, Rafizadeh S, et al.. "The Hippo Terminal Effector Yap Boosts Enterovirus Replication in Type 1 Diabetes." Nature Communications 16, no. 1 (2025): -.
Harvard	Geravandi S et al. (2025) 'The Hippo Terminal Effector Yap Boosts Enterovirus Replication in Type 1 Diabetes', Nature Communications, 16(1), pp. -.
Vancouver	Geravandi S, Liu H, Pahwa H, Madduri MK, Atawneh F, Miraki Feriz A, et al.. The Hippo Terminal Effector Yap Boosts Enterovirus Replication in Type 1 Diabetes. Nature Communications. 2025;16(1):-.
BibTex	@article{ author = {Geravandi S and Liu H and Pahwa H and Madduri MK and Atawneh F and Miraki Feriz A and Rafizadeh S and Kruf AE and Khazaei M and Bahrami P and Gotti D and Elawour M and Elgamal RM and Grasso AM and Bund D and Lupse B and Azizi Z and Zabad O and Bouzakri K and Horwitz M and Pugliese A and Maedler K and Ardestani A}, title = {The Hippo Terminal Effector Yap Boosts Enterovirus Replication in Type 1 Diabetes}, journal = {Nature Communications}, volume = {16}, number = {1}, pages = {-}, year = {2025} }
RIS	TY - JOUR AU - Geravandi S AU - Liu H AU - Pahwa H AU - Madduri MK AU - Atawneh F AU - Miraki Feriz A AU - Rafizadeh S AU - Kruf AE AU - Khazaei M AU - Bahrami P AU - Gotti D AU - Elawour M AU - Elgamal RM AU - Grasso AM AU - Bund D AU - Lupse B AU - Azizi Z AU - Zabad O AU - Bouzakri K AU - Horwitz M AU - Pugliese A AU - Maedler K AU - Ardestani A TI - The Hippo Terminal Effector Yap Boosts Enterovirus Replication in Type 1 Diabetes JO - Nature Communications VL - 16 IS - 1 SP - EP - PY - 2025 ER -

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