4.8 Article

Distinct SARS-CoV-2 RNA fragments activate Toll-like receptors 7 and 8 and induce cytokine release from human macrophages and microglia

Related references

Note: Only part of the references are listed.
Review Cell Biology

Mechanisms of SARS-CoV-2 entry into cells

Cody B. Jackson et al.

Summary: The entry of SARS-CoV-2 into host cells is facilitated by the interaction between the viral spike protein and ACE2, leading to virus-cell membrane fusion, which has been extensively studied at the structural and cellular levels worldwide. This understanding has paved the way for the development of effective vaccines in response to the COVID-19 pandemic, caused by the infection with SARS-CoV-2.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2022)

Article Cell Biology

Microglia/macrophage-derived human CCL18 promotes glioma progression via CCR8-ACP5 axis analyzed in humanized slice model

Yimin Huang et al.

Summary: This study investigates the role of factors released from glioma-associated microglia/macrophages (GAMs) in the progression of glioblastoma multiforme (GBM). Using a humanized glioma model, it is found that CCL18 promotes glioma cell growth and invasion through the functional receptor CCR8 and downstream signaling cascade involving ACP5. The results suggest that microglia/macrophage-derived CCL18 contributes to glioma growth.

CELL REPORTS (2022)

Article Medicine, General & Internal

Microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in SARS-CoV-2 hamster model

Christopher Kaufer et al.

Summary: This study found that even after viral clearance, inflammatory responses and abnormal protein accumulation can occur in the brain, which may contribute to the neurological dysfunction observed in post-COVID-19 syndrome.

EBIOMEDICINE (2022)

Article Microbiology

SARS-CoV-2 Infection of Microglia Elicits Proinflammatory Activation and Apoptotic Cell Death

Gi Uk Jeong et al.

Summary: Recent studies have shown that patients with COVID-19 may experience neurological and cognitive effects months after viral infection. Our research highlights the role of microglia-mediated neurological disorders in COVID-19 and suggests potential treatment strategies.

MICROBIOLOGY SPECTRUM (2022)

Review Immunology

What SARS-CoV-2 does to our brains

Tom Aschman et al.

Summary: There is still a lack of conclusive evidence showing that SARS-CoV-2 can directly infect brain cells. Therefore, research should focus on the host's immune response to understand the neurocognitive symptoms associated with the infection.

IMMUNITY (2022)

Review Pharmacology & Pharmacy

Toll-like receptor (TLRs) agonists and antagonists for COVID-19 treatments

Zhi-Mei Liu et al.

Summary: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) quickly infects humans and animals, causing the global epidemic of coronavirus disease 2019 (COVID-19) in 2020. By analyzing data from other coronaviruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV), we can gain insights into the mutation of SARS-CoV-2 and the prevention and treatment of COVID-19. Toll-like receptors (TLRs), as pattern recognition receptors (PRRs), play an indispensable role in identifying invaders and activating the innate immune system. Different TLRs may have varying effects on the pathogenic processes of SARS-CoV-2 in COVID-19 infection. Therefore, understanding the involvement of TLRs in the pathogenic processes of SARS-CoV-2 is of great significance for the development of treatment and prevention strategies.

FRONTIERS IN PHARMACOLOGY (2022)

Review Immunology

Regulation of the nucleic acid-sensing Toll-like receptors

Nicholas A. Lind et al.

Summary: Activation of nucleic acid-sensing Toll-like receptors is finely tuned to distinguish between self and foreign nucleic acids. The ligands for TLRs are mostly unique to microorganisms, but a subset can recognize nucleic acids present in both host and foreign microorganisms, potentially leading to self-recognition and autoimmune diseases. Research in defining the regulatory mechanisms for proper discrimination between foreign and self-nucleic acids by TLRs has revealed a complex array of mechanisms, categorized into compartmentalization, ligand availability, receptor expression, and signal transduction.

NATURE REVIEWS IMMUNOLOGY (2022)

Article Pharmacology & Pharmacy

Phase 1 study in healthy participants of the safety, pharmacokinetics, and pharmacodynamics of enpatoran (M5049), a dual antagonist of toll-like receptors 7 and 8

Andreas Port et al.

Summary: This study evaluated the safety, pharmacokinetics, and pharmacodynamics of a new toll-like receptor 7 and 8 dual antagonist, enpatoran, in healthy participants. Results indicated that enpatoran was well tolerated at both single and multiple oral doses, with inhibitory effects on interleukin-6 secretion. Further investigation of enpatoran is warranted for potential treatment of diseases driven by TLR7/8 overactivation.

PHARMACOLOGY RESEARCH & PERSPECTIVES (2021)

Article Multidisciplinary Sciences

The coding capacity of SARS-CoV-2

Yaara Finkel et al.

Summary: A high-resolution map of coding regions in the SARS-CoV-2 genome enables the identification of 23 unannotated open reading frames and quantification of the expression of canonical viral open reading frames.

NATURE (2021)

Article Biochemistry & Molecular Biology

SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis

Armin Bayati et al.

Summary: SARS-CoV-2 uses spike glycoprotein for initial interaction with cell surface and undergoes clathrin-mediated endocytosis, transferring viral RNA to cell cytosol. Knockdown of clathrin heavy chain reduces viral infectivity, highlighting the importance of clathrin-mediated endocytosis in virus infectivity.

JOURNAL OF BIOLOGICAL CHEMISTRY (2021)

Article Immunology

Neuroinvasion of SARS-CoV-2 in human and mouse brain

Eric Song et al.

Summary: The study showed through three approaches that SARS-CoV-2 is capable of infecting brain neurons, leading to metabolic changes and pathological features without triggering type I interferon responses. These results provide evidence for the neuroinvasive capacity of SARS-CoV-2 and the unexpected consequence of direct infection of neurons by the virus.

JOURNAL OF EXPERIMENTAL MEDICINE (2021)

Article Neurosciences

Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19

Jenny Meinhardt et al.

Summary: The study demonstrates the presence of SARS-CoV-2 in the nasopharynx and brain, suggesting the virus may enter the CNS through the olfactory mucosa. The virus utilizes the neural-mucosal interface in the olfactory mucosa to penetrate the nervous system, affecting various neuroanatomical areas, including the primary respiratory and cardiovascular control center.

NATURE NEUROSCIENCE (2021)

Article Microbiology

Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2

Tianling Ou et al.

Summary: Chloroquine and hydroxychloroquine have been shown to inhibit viral infection by targeting different pathways through which the SARS-CoV-2 spike protein is activated. SARS-CoV-2 relies more on the TMPRSS2 pathway for entry, while the presence of a furin-cleavage site in its spike protein further complicates the treatment with hydroxychloroquine alone. Combining hydroxychloroquine with a TMPRSS2 inhibitor may provide a more effective strategy to block SARS-CoV-2 infection.

PLOS PATHOGENS (2021)

Article Clinical Neurology

Intrathecal inflammatory responses in the absence of SARS-CoV-2 nucleic acid in the CSF of COVID-19 hospitalized patients

Erica Normandin et al.

Summary: No SARS-CoV-2 RNA was detected in the CSF of COVID-19 patients, but proinflammatory markers were found in some patients, which is atypical for neurotropic pathogens.

JOURNAL OF THE NEUROLOGICAL SCIENCES (2021)

Article Immunology

Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions

Marius Schwabenland et al.

Summary: The study found profound neuroinflammation in COVID-19 patients, with activation of innate and adaptive immune cells. These pathological changes are associated with systemic inflammation and disturbed hemostasis, suggesting potential therapeutic strategies.

IMMUNITY (2021)

Article Immunology

TLR7 Ligation Inhibits TLR8 Responsiveness in IL-27-Primed Human THP-1 Monocytes and Macrophages

Natalya Odoardi et al.

Summary: Regulation of proinflammatory cytokine expression is crucial in ssRNA virus infections. IL-27 has a modulatory role on TLR7 and TLR8 responses, enhancing TLR7 expression and TLR8-mediated cytokine secretion. Additionally, TLR7 agonist can inhibit cytokine and chemokine production induced by a TLR8 agonist.

JOURNAL OF INNATE IMMUNITY (2021)

Editorial Material Cell Biology

SARS-CoV-2 targets MAVS for immune evasion

Alessia Zotta et al.

Summary: A new study has shown that the SARS-CoV-2 nucleocapsid protein can suppress the antiviral response by directly interacting with the signalling adaptor protein MAVS. Targeting this pathway could be a promising therapeutic strategy to enhance immunity against COVID-19.

NATURE CELL BIOLOGY (2021)

Article Multidisciplinary Sciences

The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-I

Yiwen Zhang et al.

Summary: COVID-19, caused by SARS-CoV-2, significantly differs from SARS in its clinical and pathological characteristics. The viral protein ORF8 of SARS-CoV-2 interacts with MHC-I molecules, leading to their down-regulation and impairment of antigen presentation system, proposing ORF8 inhibition as a potential strategy for improving immune surveillance.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

Article Biochemistry & Molecular Biology

Structure-aware machine learning identifies microRNAs operating as Toll-like receptor 7/8 ligands

Martin Raden et al.

Summary: The study introduced a machine learning approach called BrainDead to identify the role of miRNAs as TLR ligands. Experimental validation confirmed the predicted functional activity of high- and low-scoring miRNAs, with some linked to Alzheimer's disease. The results offer new insights into the mechanisms of how miRNAs act as TLR ligands.

RNA BIOLOGY (2021)

Article Immunology

X-linked recessive TLR7 deficiency in ∼1% of men under 60 years old with life-threatening COVID-19

Takaki Asano et al.

Summary: A study revealed that rare X-linked TLR7 variants were found in 16 unrelated male individuals with critical COVID-19 pneumonia out of a cohort of 1202 male patients. No such variants were detected in 331 asymptomatic or mildly infected male individuals.

SCIENCE IMMUNOLOGY (2021)

Article Medicine, Research & Experimental

SARS-CoV-2-associated ssRNAs activate inflammation and immunity via TLR7/8

Valentina Salvi et al.

Summary: The inflammatory and IFN pathways of innate immunity are crucial in the resistance and pathogenesis of COVID-19. Single-stranded RNA fragments from the SARS-CoV-2 genome were identified as direct activators of endosomal TLR7/8 and MyD88 pathway, inducing human DC activation and inflammatory responses. The virus endosomal processing products can potentiate IFN and inflammatory responses, playing a key role in host resistance and COVID-19 pathogenesis.

JCI INSIGHT (2021)

Article Medicine, General & Internal

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

Chaolin Huang et al.

LANCET (2020)

Article Neurosciences

Single-nucleus RNA-seq identifies Huntington disease astrocyte states

Osama Al-Dalahmah et al.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2020)

Article Infectious Diseases

A first case of meningitis/encephalitis associated with SARS-Coronavirus-2

Takeshi Moriguchi et al.

INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES (2020)

Letter Clinical Neurology

Characteristics of ischaemic stroke associated with COVID-19

Rahma Beyrouti et al.

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY (2020)

Letter Medicine, General & Internal

Neurologic Features in Severe SARS-CoV-2 Infection

Julie Helms et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

Review Immunology

COVID-19: Immunology and treatment options

Susanna Felsenstein et al.

CLINICAL IMMUNOLOGY (2020)

Review Immunology

RNase T2 in Inflammation and Cancer: Immunological and Biological Views

Lei Wu et al.

FRONTIERS IN IMMUNOLOGY (2020)

Article Medicine, General & Internal

Presence of Genetic Variants Among Young Men With Severe COVID-19

Caspar I. van der Made et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2020)

Article Environmental Sciences

Imiquimod - A toll like receptor 7 agonist - Is an ideal option for management of COVID 19

Athina Angelopoulou et al.

ENVIRONMENTAL RESEARCH (2020)

Article Multidisciplinary Sciences

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Qian Zhang et al.

SCIENCE (2020)

Article Multidisciplinary Sciences

Structural analysis reveals TLR7 dynamics underlying antagonism

Shingo Tojo et al.

NATURE COMMUNICATIONS (2020)

Article Cell Biology

A Single-Cell RNA Expression Map of Human Coronavirus Entry Factors

Manvendra Singh et al.

CELL REPORTS (2020)

Article Biochemistry & Molecular Biology

β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway

Sourish Ghosh et al.

Article Medicine, Research & Experimental

Human endogenous retrovirus HERV-K(HML-2) RNA causes neurodegeneration through Toll-like receptors

Paul Dembny et al.

JCI INSIGHT (2020)

Article Biochemistry & Molecular Biology

TLR8 Is a Sensor of RNase T2 Degradation Products

Wilhelm Greulich et al.

Article Biochemical Research Methods

INTARNAHELIX-composing RNA-RNA interactions from stable inter-molecular helices boosts bacterial sRNA target prediction

Rick Gelhausen et al.

JOURNAL OF BIOINFORMATICS AND COMPUTATIONAL BIOLOGY (2019)

Review Immunology

Microglia and macrophages in brain homeostasis and disease

Qingyun Li et al.

NATURE REVIEWS IMMUNOLOGY (2018)

Article Biochemistry & Molecular Biology

IntaRNA 2.0: enhanced and customizable prediction of RNA-RNA interactions

Martin Mann et al.

NUCLEIC ACIDS RESEARCH (2017)

Article Immunology

Guanosine and its modified derivatives are endogenous ligands for TLR7

Takuma Shibata et al.

INTERNATIONAL IMMUNOLOGY (2016)

Article Biochemistry & Molecular Biology

Toll-like receptor 8 senses degradation products of single-stranded RNA

Hiromi Tanji et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2015)

Article Biochemistry & Molecular Biology

Toll-like receptor 8 senses degradation products of single-stranded RNA

Hiromi Tanji et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2015)

Article Biochemical Research Methods

ViennaRNA Package 2.0

Ronny Lorenz et al.

ALGORITHMS FOR MOLECULAR BIOLOGY (2011)

Article Hematology

TLR8-dependent TNF-α overexpression in Fanconi anemia group C cells

Scott M. Vanderwerf et al.

BLOOD (2009)

Article Immunology

TLR7 is involved in sequence-specific sensing of single-stranded RNAs in human macrophages

Michael P. Gantier et al.

JOURNAL OF IMMUNOLOGY (2008)

Review Biochemistry & Molecular Biology

Pathogen recognition and innate immunity

S Akira et al.

Article Clinical Neurology

Broad expression of Toll-like receptors in the human central nervous system

M Bsibsi et al.

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY (2002)