ArticlePLoS pathogens2014
The HIV-1 envelope transmembrane domain binds TLR2 through a distinct dimerization motif and inhibits TLR2-mediated responses.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
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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.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- MGL/CLEC10A is an important C-type lectin receptor activated in the innate immune response toFrontiers in immunology · 2025Article
- Second site reversion of HIV-1 envelope protein baseplate mutations maps to the matrix protein.Journal of virology · 2024Article
- Toll-like Receptor 2 Mediated Immune Regulation in Simian Immunodeficiency Virus-Infected Rhesus Macaques.Vaccines · 2023Article
- Toll-like Receptor Response to Human Immunodeficiency Virus Type 1 or Co-Infection with Hepatitis B or C Virus: An Overview.International journal of molecular sciences · 2023Review
- Scratching the Surface Takes a Toll: Immune Recognition of Viral Proteins by Surface Toll-like Receptors.Viruses · 2022Review
- The Role of Toll-Like Receptors in Retroviral Infection.Microorganisms · 2020Review
- Viral Membrane Fusion and the Transmembrane Domain.Viruses · 2020Review
- Characterization of Leukocytes From HIV-ART Patients Using Combined Cytometric Profiles of 72 Cell Markers.Frontiers in immunology · 2019Article
- The Role of the Small Export Apparatus Protein, SctS, in the Activity of the Type III Secretion System.Frontiers in microbiology · 2019Article
- HIV-1 Envelope Glycoproteins Induce the Production of TNF-α and IL-10 in Human Monocytes by Activating Calcium Pathway.Scientific reports · 2018Article
- Evidence that RNA Viruses Drove Adaptive Introgression between Neanderthals and Modern Humans.Cell · 2018Article
- The Third Transmembrane Domain of EscR Is Critical for Function of the EnteropathogenicmSphere · 2018Article
- The HTLV-1 gp21 fusion peptide inhibits antigen specific T-cell activation in-vitro and in mice.PLoS pathogens · 2018Article
- Role of the HIV-1 envelope transmembrane domain in intracellular sorting.BMC cell biology · 2018Article
- Variants in the non-coding region of the TLR2 gene associated with infectious subphenotypes in pediatric sickle cell anemia.Immunogenetics · 2018Article
- TLR7/8 agonist induces a post-entry SAMHD1-independent block to HIV-1 infection of monocytes.Retrovirology · 2016Article
- The Atomic Structure of the HIV-1 gp41 Transmembrane Domain and Its Connection to the Immunogenic Membrane-proximal External Region.The Journal of biological chemistry · 2015Article
- Article
Corrections and comments
- Erratum issuedSchwarzter, Roland [corrected to Schwarzer, Roland]
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HIV-1 uses a number of means to manipulate the immune system, to avoid recognition and to highjack signaling pathways. HIV-1 infected cells show limited Toll-Like Receptor (TLR) responsiveness via as yet unknown mechanisms. Using biochemical and biophysical approaches, we demonstrate that the trans-membrane domain (TMD) of the HIV-1 envelope (ENV) directly interacts with TLR2 TMD within the membrane milieu. This interaction attenuates TNFα, IL-6 and MCP-1 secretion in macrophages, induced by natural ligands of TLR2 both in in vitro and in vivo models. This was associated with decreased levels of ERK phosphorylation. Furthermore, mutagenesis demonstrated the importance of a conserved GxxxG motif in driving this interaction within the membrane milieu. The administration of the ENV TMD in vivo to lipotechoic acid (LTA)/Galactosamine-mediated septic mice resulted in a significant decrease in mortality and in tissue damage, due to the weakening of systemic macrophage activation. Our findings suggest that the TMD of ENV is involved in modulation of the innate immune response during HIV infection. Furthermore, due to the high functional homology of viral ENV proteins this function may be a general character of viral-induced immune modulation.
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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.