ArticlePloS one2012
Human cytomegalovirus induces TLR4 signaling components in monocytes altering TIRAP, TRAM and downstream interferon-beta and TNF-alpha expression.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
32 citing papers in PubMed, 44 citations in OpenAlex.
- IL-12-producing monocytes and HLA-E control HCMV-driven NKG2C+ NK cell expansion.The Journal of clinical investigation · 2014Trial
- A Potent Inhibitor of Human Cytomegalovirus Infection Works Post-Entry Specifically in Differentiating Myelo-Monocytic Cells.Pathogens (Basel, Switzerland) · 2026Article
- The HCMV tegument protein UL88 degrades MyD88 and reduces innate immune activation.Journal of virology · 2025Article
- Role of TLR4 Asp299Gly and Thr399Ile Gene Polymorphisms as a Risk Factor in Human Cytomegalovirus Positive Pregnant Women.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Viruses Binding to Host Receptors Interacts with Autophagy.International journal of molecular sciences · 2023Review
- Article
- Association between single nucleotide polymorphisms and viral load in congenital cytomegalovirus infection.Journal of mother and child · 2021Article
- Human Cytomegalovirus-Encoded microRNAs Can Be Found in Saliva Samples from Renal Transplant Recipients.Non-coding RNA · 2020Article
- Toll-Like Receptor Signaling in Depression.Psychoneuroendocrinology · 2020Review
- Article
- The Differentiation of Human Cytomegalovirus Infected-Monocytes Is Required for Viral Replication.Frontiers in cellular and infection microbiology · 2020Review
- Is the presence of HCMV components in CNS tumors a glioma-specific phenomenon?Virology journal · 2019Article
- Innate Sensing of DNA Virus Genomes.Annual review of virology · 2018Review
- The Interplay between Human Cytomegalovirus and Pathogen Recognition Receptor Signaling.Viruses · 2018Review
- LPS promotes a monocyte phenotype permissive for human cytomegalovirus immediate-early gene expression upon infection but not reactivation from latency.Scientific reports · 2017Article
- Toll-like receptors genes polymorphisms and the occurrence of HCMV infection among pregnant women.Virology journal · 2017Article
- Role of cytomegalovirus on the maturation and function of monocyte derived dendritic cells of liver transplant patients.World journal of transplantation · 2016Article
- The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability.Molecular neurobiology · 2016Review
- Monocyte Phenotype and Polyfunctionality Are Associated With Elevated Soluble Inflammatory Markers, Cytomegalovirus Infection, and Functional and Cognitive Decline in Elderly Adults.The journals of gerontology. Series A, Biological sciences and medical sciences · 2016Article
- Cytomegalovirus Enterocolitis in Immunocompetent Young Children: A Report of Two Cases and Review of the Literature.The Pediatric infectious disease journal · 2016Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Using TLR pathways, primary human cytomegalovirus (HCMV) induces innate responses including the production of inflammatory cytokines. Mounting evidence suggests that LPS recognition by TLR4/MD2/CD14 results in differential utilization of TIRAP-TRAF6 and TRAM-TRIF signaling, thereby leading to transcriptional activation of various cytokine genes. However, relative roles of the TLR4/MD2/CD14 complex and its adaptor proteins TIRAP and TRAM involved in regulating monocyte responses to HCMV are incomplete. Here, we provided evidence supporting the notion that the TLR4/MD2/CD14 complex contributes notably to HCMV-induced signaling and subsequent cytokine production in monocytes. In particular, induction of both IL-6 and IL-8 is associated with elevated TIRAP and reduced TRAM mRNA expression. The latter may serve in a compensatory pathway that yields a robust IFN response when TIRAP signaling is blocked in monocytes incubated with Toledo strain HCMV. Inhibitory studies using antisense oligonucleotides or neutralizing antibodies indicate that IL-6 induction by TLR4/MD2 complex is important for the activation of endogenous CD14 which later acts in concert or synergy with TLR4/MD2 as a factor resulting in IL-8 gene expression. We further show that exogenous recombinant CD14 can potentiate innate immune response via TLR4-dependent and possibly via TLR9-dependent pathways to promote enhanced expression/production of IL-8 and IFN-β, respectively.
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Registered trials
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.