interferon kappa / Shanghai Public Health Clinical Center - LARVOL DELTA

Prevalence of neutralizing autoantibodies against type I interferon in dengue patients. (PubMed, J Hum Immun) - "IFN-I NAbs were correlated with clinical parameters of myocardial injury and plasma leakage, with increased odds ratio (OR) for cardiac injury (OR = 22.8, P = 0.003) and hypoproteinemia (OR = 53.5, P = 0.001). These findings suggest that IFN-I NAbs may contribute to severe clinical manifestations of dengue, warranting validation in larger cohorts."

Journal • Dengue Fever • Hematological Disorders • Infectious Disease

HCMV-pUS2 Disrupts cGAS-STING Signaling through LMAN2L Degradation. (PubMed, PLoS Pathog) - "LMAN2L knockout diminishes HCMV-induced expression of type I interferons and interferon-stimulated genes...Though it does not affect STING dimerization or TBK1 recruitment, it is essential for STING translocation from the ER to the Golgi. Our findings uncover LMAN2L as a novel host regulator of the STING pathway and identify pUS2-mediated ERAD as a previously unrecognized viral immune evasion strategy."

Journal • Cytomegalovirus Infection • Infectious Disease • Targeted Protein Degradation

Hydroxylation of the HIV-1 antisense protein promotes immune evasion of HIV-1 via modulation of TBK1. (PubMed, Nat Commun) - "Here we show that the HIV-1 antisense protein (ASP) evades host immunity by interfering with the type I interferon (IFN-I) response...In humanized mice, either ASP deletion or treatment with the RNF114 inhibitor EN219 or the PHD3 inhibitor Molidustat enhances antiviral immunity and reduces viral replication. Clinically, RNF114 and PHD3 transcript levels exhibit a positive correlation with viral load in treatment-naive patients. Here we show a distinct HIV-1 immune evasion mechanism involving proline hydroxylation and K6-linked ubiquitination, highlighting therapeutic potential."

Journal • Human Immunodeficiency Virus • Infectious Disease • Targeted Protein Degradation • RNF114

Linker histone H1.2 inhibits HSV-1-induced IFN response via cGAS. (PubMed, mBio) - "Moreover, HSV-1 infection downregulates H1.2 expression by reducing the mRNA levels of its transcription factor Sp1, thus allowing cGAS release to activate type I interferon signaling...We revealed the mechanism of host cells regulating antiviral immunity through the Sp1-H1.2-cGAS axis and found plicamycin could be used as a potential anti-infective drug. These data may offer important reference value for innate immune research."

Journal • Infectious Disease • CGAS • TRIM28

HSPA2 modulates antiviral immunity by inhibiting TBK1 activation. (PubMed, Cell Rep) - "The production of type I interferons (IFN-I) induced by viruses is critical for the host to resist viral infection...Mechanistically, HSPA2 binds to TBK1 and competes with the HECT and RLD domains containing E3 ubiquitin protein ligase 5 (HERC5) for TBK1 binding, thereby abrogating HERC5-dependent K63-linked ubiquitination of TBK1 at lysine 608 (K608), which disrupts the formation of TBK1-associated complexes and suppresses the subsequent dimerization and nuclear translocation of interferon regulatory factor 3 (IRF3), ultimately blocking IFN-I production. This study provides insights into the regulatory network governing innate immune homeostasis and identifies HSPA2 as a potential target for antiviral therapy."

Journal • Infectious Disease • Targeted Protein Degradation • UBR5

Hippo kinase NDR1 crosstalks with GSK3 and positively regulates type I interferon-mediated antiviral innate immunity. (PubMed, Mol Immunol) - "These mechanistic defects are mirrored in vivo, as NDR1-deficient mice exhibit impaired systemic IFN-β responses and markedly heightened susceptibility to viral infection. Together, our findings establish a previously unappreciated NDR1-GSK3-STAT1 signalling axis that integrates Hippo pathway components into antiviral innate immunity and reveal NDR1 as a potential target for enhancing host resistance to viral pathogens."

Journal • Infectious Disease • IFNB1 • NDRG1

ID1 boosts antiviral immunity by countering PRMT5-mediated STING methylation. (PubMed, Cell Rep) - "The stimulator of interferon genes (STING) is a vital protein for the activation of the type I interferon signaling pathway. Importantly, EPZ015666, a selective PRMT5 inhibitor, substantially enhanced antiviral immune responses in vivo and in vitro. These findings unveil an unreported regulatory mechanism in which ID1 and PRMT5 modulate STING activity and highlight EPZ015666 as a promising therapeutic candidate for antiviral interventions."

Journal • Infectious Disease • ID1 • STING

Efficacy and safety of interferon alpha-2b aerosol therapy for patients infected with the SARS-CoV-2 omicron variant: A randomized controlled single-blind study. (PubMed, Cell Immunol) - "The efficacy of Type I interferon (IFN) in treating COVID-19 has remained controversial...Regarding safety, there was no significant difference in the incidence of adverse reactions between the two groups during treatment. Collectively, our study suggests that Type I IFN, when administered via nebulized inhalation, may offer benefits specifically for the asymptomatic subgroup among COVID-19 patients, indicating selective efficacy."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IFNA1 • IL4

Anti-inflammatory Roles of Type I Interferon Signaling in the Lung (ATS 2024) - " Using mice deficient in type I interferon signaling (IFNAR1-/-), we demonstrate that the absence of interferon signaling resulted in a robust and persistent inflammatory response against Pseudomonas aeruginosa, lipopolysaccharide, and chemotherapeutic agent bleomycin. Our data demonstrate anti-inflammatory effects of type I interferon signaling and provide novel insights into the conserved anti-inflammatory mechanisms of the type I interferon pathway."

Fibrosis • Immunology • Infectious Disease • Inflammation • Respiratory Diseases • IFNAR1

Mycobacterial CpsA activates type I IFN signaling in macrophages via cGAS-mediated pathway. (PubMed, iScience) - "Type I interferon (IFN) production is crucial in tuberculosis pathogenesis, yet the bacterial factors initiating this process are incompletely understood...Moreover, we further show that CpsA deficiency cause decreased cytosolic DNA levels, correlating with impaired phagosomal membrane rupture. Our findings reveal a new function of mycobacterial CpsA in type I IFN production and offer insight into the molecular mechanisms underlying mycobacterial infection pathology."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Prevalence of Neutralizing Autoantibodies Against Type I Interferon in a Multicenter Cohort of Severe or Critical COVID-19 Cases in Shanghai. (PubMed, J Clin Immunol) - "The presence of type I IFN-neutralizing antibodies is a pervasive risk factor for severe/critical COVID-19 in the Chinese population."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CRP • IFNA1

SARS-COV-2 protein NSP9 promotes cytokine production by targeting TBK1. (PubMed, Front Immunol) - "Additionally, we identified Lys59 of NSP9 as a critical ubiquitin site involved in the degradation. These findings elucidate a previously unknown mechanism by which a SARS-COV-2 protein promotes cytokine storm and identifies a novel target for COVID-19 treatment."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • Targeted Protein Degradation

Transcriptomic Analysis of Mycobacterial Infected Macrophages Reveals a High MOI Specific Type I IFN Signaling. (PubMed, Infect Immun) - "KEGG pathway enrichment analysis revealed that type I interferon (IFN)-related pathways were inoculant dose-dependent and enriched only at high MOIs, whereas TNF pathways were inoculant dose-independent and enriched at all MOIs...In summary, transcriptional profiling of mycobacterial infected MΦs revealed that different MOIs activate distinct immune pathways and the type I IFN pathway is activated only at high MOIs. This study should provide guidance for selecting the MOI most appropriate for different research questions."

Journal • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Glutamylation of an HIV-1 protein inhibits the immune response by hijacking STING. (PubMed, Cell Rep) - "Cyclic GMP-AMP synthase (cGAS) recognizes Y-form cDNA of human immunodeficiency virus type 1 (HIV-1) and initiates antiviral immune response through cGAS-stimulator of interferon genes (STING)-TBK1-IRF3-type I interferon (IFN-I) signalingcascade...However, CoCl, an agonist of cytosolic carboxypeptidases (CCPs), counteracts the glutamylation of p6 at the Glu6 residue and inhibits HIV-1 immune evasion. These findings reveal a mechanism through which an HIV-1 protein mediates immune evasion and provides a therapeutic drug candidate to treat HIV-1 infection."

Journal • Human Immunodeficiency Virus • Infectious Disease • Targeted Protein Degradation • CGAS • STING • TRIM32

Revealing the characteristics of ZIKV infection through tissue-specific transcriptome sequencing analysis. (PubMed, BMC Genomics) - "Together, these data may provide a systemic insight into the pathogenesis of ZIKV infection in distinct human tissue-derived cell lines, which is likely to help develop prophylactic and therapeutic strategies against ZIKV infection."

Journal • Infectious Disease

Angiotensin-Converting Enzyme 2 Potentiates SARS-CoV-2 Infection by Antagonizing Type I Interferon Induction and Its Down-Stream Signaling Pathway. (PubMed, mSphere) - "Both full-length ACE2 and truncated dACE2 can antagonize IFN-mediated antiviral response. These findings are key to understanding the counteraction between SARS-CoV-2 pathogenicity and the host antiviral defenses."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • STAT2

HIV-1 Vif suppresses antiviral immunity by targeting STING. (PubMed, Cell Mol Immunol) - "HIV-1 infection-induced cGAS-STING-TBK1-IRF3 signaling activates innate immunity to produce type I interferon (IFN)...These findings reveal a previously unknown mechanism through which HIV-1 evades antiviral immunity via the ITIM-containing protein to inhibit the posttranslational modification of STING. These results provide a molecular basis for the development of new therapeutic strategies to treat HIV-1 infection."

Journal • Human Immunodeficiency Virus • Infectious Disease • Targeted Protein Degradation • STING

Carrier-free micellar CpG interacting with cell membrane for enhanced immunological treatment of HIV-1. (PubMed, Biomaterials) - "U4CpG treatment induced activation of plasmacytoid dendritic cells (pDCs) and natural killer (NK) cells in healthy human peripheral blood, which produced type I interferons (IFNs) and IFN-γ in human peripheral blood mononuclear cells (PBMCs)...Furthermore, U4CpG-treated PBMC cultured medium elicited transcription of latent HIV-1 in U1 cells indicating that U4CpG reversed HIV-1 latency. Thus, the functions of U4CpG in eradicating HIV-1 by enhancing immunity and reversing latency make the material a potential candidate for clinical studies dealing with viral infection."

Journal • Human Immunodeficiency Virus • Immunology • Infectious Disease • IFNG • TLR9