ArticleNature microbiology2020
Herpesviruses induce aggregation and selective autophagy of host signalling proteins NEMO and RIPK1 as an immune-evasion mechanism.
Article in Nature microbiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 59 citations in OpenAlex.
- Transglutaminase 2 regulates innate immunity: mechanisms and therapeutic implications.Oncoimmunology · 2026Review
- Herpesviruses and autophagy: An intracellular conflict.Virulence · 2026Review
- A viral APOBEC3 antagonist distinguishes HHV-6A from HHV-6B.Nature communications · 2026Article
- Mammalian innate antiviral defenses: beyond interferon.Journal of virology · 2025Review
- Poxvirus H5 mediates the formation of liquid-liquid phase separation condensates which promote virus factory assembly.PLoS pathogens · 2025Article
- Identification of Epstein-Barr virus BORF2 sequences required for APOBEC3B relocalization.Journal of virology · 2025Article
- Kaposi's sarcoma-associated herpesvirus ORF61 protein sequesters APOBEC3B in filamentous aggregates.Journal of virology · 2025Article
- A viral necrosome mediates direct RIPK3 activation to promote inflammatory necroptosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Herpes simplex virus 1 encodes a STING antagonist that can be therapeutically targeted.Cell reports. Medicine · 2025Article
- HHV-6B ribonucleotide reductase sequesters NF-κB subunit p65 to inhibit innate immune responses.iScience · 2025Article
- Review
- Review
- The multifaceted roles of selective autophagy receptors in viral infections.Journal of virology · 2024Review
- No Time to Die: How Cytomegaloviruses Suppress Apoptosis, Necroptosis, and Pyroptosis.Viruses · 2024Review
- Article
- ASFV infection induces macrophage necroptosis and releases proinflammatory cytokine by ZBP1-RIPK3-MLKL necrosome activation.Frontiers in microbiology · 2024Article
- The MGF300-2R protein of African swine fever virus is associated with viral pathogenicity by promoting the autophagic degradation of IKKα and IKKβ through the recruitment of TOLLIP.PLoS pathogens · 2023Article
- Master mitotic kinases regulate viral genome delivery during papillomavirus cell entry.Nature communications · 2023Article
- The role of autophagy in viral infections.Journal of biomedical science · 2023Review
- Article
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Viruses manipulate cellular signalling by inducing the degradation of crucial signal transducers, usually via the ubiquitin-proteasome pathway. Here, we show that the murine cytomegalovirus (Murid herpesvirus 1) M45 protein induces the degradation of two cellular signalling proteins, the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) essential modulator (NEMO) and the receptor-interacting protein kinase 1 (RIPK1), via a different mechanism: it induces their sequestration as insoluble protein aggregates and subsequently facilitates their degradation by autophagy. Aggregation of target proteins requires a distinct sequence motif in M45, which we termed 'induced protein aggregation motif'. In a second step, M45 recruits the retromer component vacuolar protein sorting 26B (VPS26B) and the microtubule-associated protein light chain 3 (LC3)-interacting adaptor protein TBC1D5 to facilitate degradation of aggregates by selective autophagy. The induced protein aggregation motif is conserved in M45-homologous proteins of several human herpesviruses, including herpes simplex virus, Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus, but is only partially conserved in the human cytomegalovirus UL45 protein. We further show that the HSV-1 ICP6 protein induces RIPK1 aggregation and degradation in a similar fashion to M45. These data suggest that induced protein aggregation combined with selective autophagy of aggregates (aggrephagy) represents a conserved viral immune-evasion mechanism.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.