ArticlePloS one2014
Activation of nucleotide oligomerization domain 2 (NOD2) by human cytomegalovirus initiates innate immune responses and restricts virus replication.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 54 citations in OpenAlex.
- Advances in gut-lung axis research: clinical perspectives on pneumonia prevention and treatment.Frontiers in immunology · 2025Review
- Overview of Cytomegalovirus Ocular Diseases: Retinitis, Corneal Endotheliitis, and Iridocyclitis.Viruses · 2024Review
- Transcription of NOD1 and NOD2 and their interaction with CARD9 and RIPK2 in IFN signaling in a perciform fish, the Chinese perch,Frontiers in immunology · 2024Article
- Inhibition of human cytomegalovirus replication by interferon alpha can involve multiple anti-viral factors.The Journal of general virology · 2023Article
- Innate immune recognition against SARS-CoV-2.Inflammation and regeneration · 2023Review
- Interactions of Autophagy and the Immune System in Health and Diseases.Autophagy reports · 2022Article
- Hcmv-miR-UL148D regulates the staurosporine-induced apoptosis by targeting the Endoplasmic Reticulum to Nucleus signaling 1(ERN1).PloS one · 2022Article
- Foot-and-Mouth Disease Virus Inhibits RIP2 Protein Expression to Promote Viral Replication.Virologica Sinica · 2021Article
- Nodosome Inhibition as a Novel Broad-Spectrum Antiviral Strategy against Arboviruses, Enteroviruses, and SARS-CoV-2.Antimicrobial agents and chemotherapy · 2021Article
- Apoptosis Disorder, a Key Pathogenesis of HCMV-Related Diseases.International journal of molecular sciences · 2021Review
- Role of NLRs in the Regulation of Type I Interferon Signaling, Host Defense and Tolerance to Inflammation.International journal of molecular sciences · 2021Review
- Regulation of Tripartite Motif-Containing Proteins on Immune Response and Viral Evasion.Frontiers in microbiology · 2021Review
- Human cytomegalovirus evades ZAP detection by suppressing CpG dinucleotides in the major immediate early 1 gene.PLoS pathogens · 2020Article
- NOD1 and NOD2 in inflammatory and infectious diseases.Immunological reviews · 2020Review
- NOD1 and NOD2 Activation by Diverse Stimuli: a Possible Role for Sensing Pathogen-Induced Endoplasmic Reticulum Stress.Infection and immunity · 2020Review
- Novel XIAP mutation causing enhanced spontaneous apoptosis and disturbed NOD2 signalling in a patient with atypical adult-onset Crohn's disease.Cell death & disease · 2020Article
- Trained immunity in organ transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020Review
- Foot-and-Mouth Disease Virus Antagonizes NOD2-Mediated Antiviral Effects by Inhibiting NOD2 Protein Expression.Journal of virology · 2019Article
- Integrin activation by the lipid molecule 25-hydroxycholesterol induces a proinflammatory response.Nature communications · 2019Article
- Genetic variations of NOD2 and MD2 genes in hepatitis B virus infection.Saudi journal of biological sciences · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nucleotide-binding oligomerization domain 2 (NOD2) is an important innate immune sensor of bacterial pathogens. Its induction results in activation of the classic NF-κB pathway and alternative pathways including type I IFN and autophagy. Although the importance of NOD2 in recognizing RNA viruses has recently been identified, its role in sensing DNA viruses has not been studied. We report that infection with human cytomegalovirus (HCMV) results in significant induction of NOD2 expression, beginning as early as 2 hours post infection and increasing steadily 24 hours post infection and afterwards. Infection with human herpesvirus 1 and 2 does not induce NOD2 expression. While the HCMV-encoded glycoprotein B is not required for NOD2 induction, a replication competent virion is necessary. Lentivirus-based NOD2 knockdown in human foreskin fibroblasts (HFFs) and U373 glioma cells leads to enhanced HCMV replication along with decreased levels of interferon beta (IFN-β) and the pro-inflammatory cytokine, IL8. NOD2 induction in HCMV-infected cells activates downstream NF-κB and interferon pathways supported by reduced nuclear localization of NF-κB and pIRF3 in NOD2 knockdown HFFs. Stable overexpression of NOD2 in HFFs restricts HCMV replication in association with increased levels of IFN-β and IL8. Similarly, transient overexpression of NOD2 in U373 cells or its downstream kinase, RIPK2, results in decreased HCMV replication and enhanced cytokine responses. However, overexpression of a mutant NOD2, 3020insC, associated with severe Crohn's disease, results in enhanced HCMV replication and decreased levels of IFN-β in U373 cells. These results show for the first time that NOD2 plays a significant role in HCMV replication and may provide a model for studies of HCMV recognition by the host cell and HCMV colitis in Crohn's disease.
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