Mystery machine: the complex roles of NLRX1 in viral infection

Effective antiviral immunity requires a delicate balance between controlling infection and preventing excessive inflammation. NLRX1, an atypical member of the NOD-like receptor family, plays a crucial regulatory role in this process by modulating immune responses to both RNA and DNA viruses. Unlike...

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Main Authors: Mackenzie K. Woolls, Carley M. Elliott, Hannah M. Ivester, Irving Coy Allen
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1581313/full
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author Mackenzie K. Woolls
Carley M. Elliott
Hannah M. Ivester
Irving Coy Allen
Irving Coy Allen
Irving Coy Allen
Irving Coy Allen
author_facet Mackenzie K. Woolls
Carley M. Elliott
Hannah M. Ivester
Irving Coy Allen
Irving Coy Allen
Irving Coy Allen
Irving Coy Allen
author_sort Mackenzie K. Woolls
collection DOAJ
description Effective antiviral immunity requires a delicate balance between controlling infection and preventing excessive inflammation. NLRX1, an atypical member of the NOD-like receptor family, plays a crucial regulatory role in this process by modulating immune responses to both RNA and DNA viruses. Unlike other NLRs, NLRX1 does not directly activate inflammatory pathways, but rather fine tunes immune responses through interactions with key signaling initiators like MAVS, FAF1, viral RNA, and FBXO6. These interactions allow NLRX1 to influence antiviral pathways in a highly context-dependent manner. In RNA virus infections, NLRX1 can either enhance immune signaling to restrict viral replication or suppress type 1 IFN responses to promote viral persistence. Similarly, in DNA viral infections, NLRX1 exerts either protective or pathogenic effects, though the precise mechanisms remain unclear. Emerging evidence suggests that NLRX1 may also serve as a key regulator of inflammation and metabolic processes during infection, further contributing to its complex role in immunity. By synthesizing current research, this review provides insight into how NLRX1 regulates immune signaling in RNA and DNA viral infections, highlighting its dynamic role in antiviral immunity and the remaining gaps in our understanding.
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spelling doaj-art-3d30e24022ad4d04a27d20792c0015cf2025-08-20T03:53:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15813131581313Mystery machine: the complex roles of NLRX1 in viral infectionMackenzie K. Woolls0Carley M. Elliott1Hannah M. Ivester2Irving Coy Allen3Irving Coy Allen4Irving Coy Allen5Irving Coy Allen6Graduate Program in Translational Biology, Medicine, and Health, Virginia Tech, Roanoke, VA, United StatesGraduate Program in Translational Biology, Medicine, and Health, Virginia Tech, Roanoke, VA, United StatesGraduate Program in Translational Biology, Medicine, and Health, Virginia Tech, Roanoke, VA, United StatesGraduate Program in Translational Biology, Medicine, and Health, Virginia Tech, Roanoke, VA, United StatesBiomedical and Veterinary Sciences Graduate Program, Virginia Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United StatesDepartment of Basic Science Education, Virginia Tech Carilion School of Medicine, Roanoke, VA, United StatesThe Virginia Tech Center for Emerging, Zoonotic and Arthropod-borne Pathogens, Virginia Tech, Blacksburg, VA, United StatesEffective antiviral immunity requires a delicate balance between controlling infection and preventing excessive inflammation. NLRX1, an atypical member of the NOD-like receptor family, plays a crucial regulatory role in this process by modulating immune responses to both RNA and DNA viruses. Unlike other NLRs, NLRX1 does not directly activate inflammatory pathways, but rather fine tunes immune responses through interactions with key signaling initiators like MAVS, FAF1, viral RNA, and FBXO6. These interactions allow NLRX1 to influence antiviral pathways in a highly context-dependent manner. In RNA virus infections, NLRX1 can either enhance immune signaling to restrict viral replication or suppress type 1 IFN responses to promote viral persistence. Similarly, in DNA viral infections, NLRX1 exerts either protective or pathogenic effects, though the precise mechanisms remain unclear. Emerging evidence suggests that NLRX1 may also serve as a key regulator of inflammation and metabolic processes during infection, further contributing to its complex role in immunity. By synthesizing current research, this review provides insight into how NLRX1 regulates immune signaling in RNA and DNA viral infections, highlighting its dynamic role in antiviral immunity and the remaining gaps in our understanding.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1581313/fullinterferonsMAVSPAMPregulatoryantiviral
spellingShingle Mackenzie K. Woolls
Carley M. Elliott
Hannah M. Ivester
Irving Coy Allen
Irving Coy Allen
Irving Coy Allen
Irving Coy Allen
Mystery machine: the complex roles of NLRX1 in viral infection
Frontiers in Immunology
interferons
MAVS
PAMP
regulatory
antiviral
title Mystery machine: the complex roles of NLRX1 in viral infection
title_full Mystery machine: the complex roles of NLRX1 in viral infection
title_fullStr Mystery machine: the complex roles of NLRX1 in viral infection
title_full_unstemmed Mystery machine: the complex roles of NLRX1 in viral infection
title_short Mystery machine: the complex roles of NLRX1 in viral infection
title_sort mystery machine the complex roles of nlrx1 in viral infection
topic interferons
MAVS
PAMP
regulatory
antiviral
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1581313/full
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