<i>Pteropus vampyrus</i> TRIM40 Is an Interferon-Stimulated Gene That Antagonizes RIG-I-like Receptors

Nipah virus (NiV; genus: Henipavirus; family: <i>Paramyxoviridae</i>) naturally infects Old World fruit bats (family <i>Pteropodidae</i>) without causing overt disease. Conversely, NiV infection in humans and other mammals can be lethal. Comparing bat antiviral responses with...

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Main Authors: Sarah van Tol, Adam Hage, Ricardo Rajsbaum, Alexander N. Freiberg
Format: Article
Language:English
Published: MDPI AG 2023-10-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/15/11/2147
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author Sarah van Tol
Adam Hage
Ricardo Rajsbaum
Alexander N. Freiberg
author_facet Sarah van Tol
Adam Hage
Ricardo Rajsbaum
Alexander N. Freiberg
author_sort Sarah van Tol
collection DOAJ
description Nipah virus (NiV; genus: Henipavirus; family: <i>Paramyxoviridae</i>) naturally infects Old World fruit bats (family <i>Pteropodidae</i>) without causing overt disease. Conversely, NiV infection in humans and other mammals can be lethal. Comparing bat antiviral responses with those of humans may illuminate the mechanisms that facilitate bats’ tolerance. Tripartite motif proteins (TRIMs), a large family of E3-ubiquitin ligases, fine-tune innate antiviral immune responses, and two human TRIMs interact with Henipavirus proteins. We hypothesize that NiV infection induces the expression of an immunosuppressive TRIM in bat, but not human cells, to promote tolerance. Here, we show that TRIM40 is an interferon-stimulated gene (ISG) in pteropodid but not human cells. Knockdown of bat TRIM40 increases gene expression of IFNβ, ISGs, and pro-inflammatory cytokines following poly(I:C) transfection. In <i>Pteropus vampyrus</i>, but not human cells, NiV induces TRIM40 expression within 16 h after infection, and knockdown of TRIM40 correlates with reduced NiV titers as compared to control cells. Bats may have evolved to express TRIM40 in response to viral infections to control immunopathogenesis.
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spelling doaj.art-af6e44ad4fe941bcb71b15c8c885f3fd2023-11-24T15:10:33ZengMDPI AGViruses1999-49152023-10-011511214710.3390/v15112147<i>Pteropus vampyrus</i> TRIM40 Is an Interferon-Stimulated Gene That Antagonizes RIG-I-like ReceptorsSarah van Tol0Adam Hage1Ricardo Rajsbaum2Alexander N. Freiberg3Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USAInstitute for Human Infections and Immunity, Sealy & Smith Foundation, University of Texas Medical Branch, Galveston, TX 77555, USANipah virus (NiV; genus: Henipavirus; family: <i>Paramyxoviridae</i>) naturally infects Old World fruit bats (family <i>Pteropodidae</i>) without causing overt disease. Conversely, NiV infection in humans and other mammals can be lethal. Comparing bat antiviral responses with those of humans may illuminate the mechanisms that facilitate bats’ tolerance. Tripartite motif proteins (TRIMs), a large family of E3-ubiquitin ligases, fine-tune innate antiviral immune responses, and two human TRIMs interact with Henipavirus proteins. We hypothesize that NiV infection induces the expression of an immunosuppressive TRIM in bat, but not human cells, to promote tolerance. Here, we show that TRIM40 is an interferon-stimulated gene (ISG) in pteropodid but not human cells. Knockdown of bat TRIM40 increases gene expression of IFNβ, ISGs, and pro-inflammatory cytokines following poly(I:C) transfection. In <i>Pteropus vampyrus</i>, but not human cells, NiV induces TRIM40 expression within 16 h after infection, and knockdown of TRIM40 correlates with reduced NiV titers as compared to control cells. Bats may have evolved to express TRIM40 in response to viral infections to control immunopathogenesis.https://www.mdpi.com/1999-4915/15/11/2147tripartite motif (TRIM) proteinsRIG-I-like receptorsMDA5RIG-INipah virus (NiV)TRIM40
spellingShingle Sarah van Tol
Adam Hage
Ricardo Rajsbaum
Alexander N. Freiberg
<i>Pteropus vampyrus</i> TRIM40 Is an Interferon-Stimulated Gene That Antagonizes RIG-I-like Receptors
Viruses
tripartite motif (TRIM) proteins
RIG-I-like receptors
MDA5
RIG-I
Nipah virus (NiV)
TRIM40
title <i>Pteropus vampyrus</i> TRIM40 Is an Interferon-Stimulated Gene That Antagonizes RIG-I-like Receptors
title_full <i>Pteropus vampyrus</i> TRIM40 Is an Interferon-Stimulated Gene That Antagonizes RIG-I-like Receptors
title_fullStr <i>Pteropus vampyrus</i> TRIM40 Is an Interferon-Stimulated Gene That Antagonizes RIG-I-like Receptors
title_full_unstemmed <i>Pteropus vampyrus</i> TRIM40 Is an Interferon-Stimulated Gene That Antagonizes RIG-I-like Receptors
title_short <i>Pteropus vampyrus</i> TRIM40 Is an Interferon-Stimulated Gene That Antagonizes RIG-I-like Receptors
title_sort i pteropus vampyrus i trim40 is an interferon stimulated gene that antagonizes rig i like receptors
topic tripartite motif (TRIM) proteins
RIG-I-like receptors
MDA5
RIG-I
Nipah virus (NiV)
TRIM40
url https://www.mdpi.com/1999-4915/15/11/2147
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