Selective TLR ligand stimulation enhances in vivo mosquito-borne flavivirus pathogenicity.

Mosquito saliva facilitates pathogen transmission and enhances the severity of diseases caused by mosquito-borne viruses; however, the underlying mechanisms are unknown. Here, we demonstrate that mosquito salivary gland extracts (SGEs) enhance flaviviral pathogenicity in vivo by activating innate immune responses following the accumulation of immune cells at the infection site. Among the innate immune signaling pathways, the TLR2 pathway enhances flaviviral pathogenicity in a manner similar to that of SGEs.

SFTSV utilizes AXL/GAS6 for entry via PI3K-PLC-dependent macropinocytosis activated by AXL-kinase.

Severe fever with thrombocytopenia syndrome (SFTS) is a significant public health concern caused by SFTS virus (SFTSV), a tick-borne RNA virus. Previous studies have identified DC-SIGN and related C-type lectins as receptors of SFTSV infection in specific cell populations. Our genome-wide CRISPR activation screening identified AXL, a receptor tyrosine kinase, as a novel entry receptor for SFTSV.

Establishment of a green fluorescent protein (GFP)-based reporter for picornaviral 3C proteases.

Picornaviruses represent a diverse group of plus-stranded RNA viruses, many of which have been linked to severe diseases in both humans and animals. The viral 3C protease is essential for the maturation of viral proteins and the propagation of picornaviruses and, owing to its cleavage activity against multiple host proteins, is associated with the pathogenesis of picornaviruses. The picornaviral 3C protease is an ideal drug target for inhibiting viral propagation and mitigating pathogenesis; however, methodology to evaluate and compare the activity of phylogenetically diverse proteases remains lacking.

Development of in vitro plaque-based assay for assessment of antibody-dependent enhancement in SARS-CoV-2 infection.

Antibody-dependent enhancement (ADE) of infection is a concerning phenomenon in SARS-CoV-2 infection, since it may develop disease severity. Although ADE has been demonstrated in animal models, the pathogenic mechanism has not been fully elucidated. The present study aimed to develop a simple assay system for detecting SARS-CoV-2 ADE activity in any antibody specimen.

Modulating Immunogenicity and Reactogenicity in mRNA-Lipid Nanoparticle Vaccines through Lipid Component Optimization.

Messenger RNA (mRNA) vaccines effectively induce antibody production and T cell responses. However, adverse reactions, such as fatigue and fever, following administration remain a key challenge. To modulate the immunogenicity and reactogenicity of mRNA vaccines, the optimization of lipid nanoparticle (LNP) formulations has been attempted, particularly by screening ionizable lipids.

Evolutionary dynamics of heparan sulfate utilization by SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants have acquired enhanced infectivity compared to earlier variants. To elucidate the underlying molecular mechanisms, we conducted CRISPR library screening to identify cell surface molecules that interact with the Omicron spike protein. Our findings revealed a significantly higher affinity between the Omicron spike and cell surface heparan sulfate compared to the wild-type spike.

Construction of a variable fragment (Fv)-immunoglobulin A (IgA) anti-receptor binding domain (RBD) SARS-CoV-2 library based on IgA from Indonesian COVID-19 survivors.

Despite entering the post-pandemic phase, SARS-CoV-2 remains a treatment challenge due to evolving mutations and immune evasion, leading to the emergence of antibody-resistant variants. This study aims to computationally construct a human Fv against various emerged variants of SARS-CoV-2 based on IgA sequences from Indonesian COVID-19 survivors. Survivor's saliva and plasma were purified using affinity chromatography to isolate anti-SARS-CoV-2 IgA.

Hypertonic intranasal vaccines gain nasal epithelia access to exert strong immunogenicity.

Intranasal vaccines potentially offer superior protection against viral infections compared with injectable vaccines. The immunogenicity of intranasal vaccines including adenovirus vector (AdV), has room for improvement, while few options are available for safe execution. In this study, we demonstrate that modifying a basic parameter of vaccine formulation, i.

NEDD4-binding protein 1 suppresses hepatitis B virus replication by regulating viral RNAs.

Chronic infection with hepatitis B virus (HBV) (chronic HBV infection) places patients at increased risk for liver cirrhosis and hepatocellular carcinoma. Although nucleos(t)ide analogues are mainly used for the treatment of HBV, they require long-term administration and may lead to the emergence of drug-resistant mutants. Therefore, to identify targets for the development of novel anti-HBV drugs, we screened for HBV-suppressive host factors using a plasmid expression library of RNA-binding proteins (RBPs).

Targeted labeling and depletion of alveolar macrophages using VeDTR mouse technology.

Alveolar macrophages (AMs) are essential for maintaining lung homeostasis. However, their roles in respiratory infections have been controversial because the methods of depleting them have often suffered from poor cell selectivity. To resolve this problem, we here used VeDTR technology to generate a transgenic mouse line in which AMs can be specifically depleted using diphtheria toxin.

BCR, not TCR, repertoire diversity is associated with favorable COVID-19 prognosis.

Introduction: The SARS-CoV-2 pandemic has had a widespread and severe impact on society, yet there have also been instances of remarkable recovery, even in critically ill patients.

Materials And Methods: In this study, we used single-cell RNA sequencing to analyze the immune responses in recovered and deceased COVID-19 patients during moderate and critical stages.

Results: Expanded T cell receptor (TCR) clones were predominantly SARS-CoV-2-specific, but represented only a small fraction of the total repertoire in all patients.

HCV infection activates the proteasome via PA28γ acetylation and heptamerization to facilitate the degradation of RNF2, a catalytic component of polycomb repressive complex 1.

We previously reported that hepatitis C virus (HCV) infection or HCV core protein expression induces HOX gene expression by impairing histone H2A monoubiquitination via a proteasome-dependent reduction in the level of RNF2, a key catalytic component of polycomb repressive complex 1 (H. Kasai, K. Mochizuki, T.

Clonal landscape of autoantibody-secreting plasmablasts in COVID-19 patients.

Whereas severe COVID-19 is often associated with elevated autoantibody titers, the underlying mechanism behind their generation has remained unclear. Here we report clonal composition and diversity of autoantibodies in humoral response to SARS-CoV-2. Immunoglobulin repertoire analysis and characterization of plasmablast-derived monoclonal antibodies uncovered clonal expansion of plasmablasts producing cardiolipin (CL)-reactive autoantibodies.

Regulation viral RNA transcription and replication by higher-order RNA structures within the nsp1 coding region of MERS coronavirus.

Coronavirus (CoV) possesses numerous functional cis-acting elements in its positive-strand genomic RNA. Although most of these RNA structures participate in viral replication, the functions of RNA structures in the genomic RNA of CoV in viral replication remain unclear. In this study, we investigated the functions of the higher-order RNA stem-loop (SL) structures SL5B, SL5C, and SL5D in the ORF1a coding region of Middle East respiratory syndrome coronavirus (MERS-CoV) in viral replication.

Importin-7-dependent nuclear translocation of the Flavivirus core protein is required for infectious virus production.

Flaviviridae is a family of positive-stranded RNA viruses, including human pathogens, such as Japanese encephalitis virus (JEV), dengue virus (DENV), Zika virus (ZIKV), and West Nile virus (WNV). Nuclear localization of the viral core protein is conserved among Flaviviridae, and this feature may be targeted for developing broad-ranging anti-flavivirus drugs. However, the mechanism of core protein translocation to the nucleus and the importance of nuclear translocation in the viral life cycle remain unknown.

Enterovirus 3A protein disrupts endoplasmic reticulum homeostasis through interaction with GBF1.

Enteroviruses are single-stranded, positive-sense RNA viruses causing endoplasmic reticulum (ER) stress to induce or modulate downstream signaling pathways known as the unfolded protein responses (UPR). However, viral and host factors involved in the UPR related to viral pathogenesis remain unclear. In the present study, we aimed to identify the major regulator of enterovirus-induced UPR and elucidate the underlying molecular mechanisms.

Akaluc bioluminescence offers superior sensitivity to track dynamics of SARS-CoV-2 infection.

Monitoring viral dynamics can improve our understanding of pathogenicity and tissue tropism. Because the gene size of RNA viruses is typically small, NanoLuc is the primary choice for accommodation within viral genome. However, NanoLuc/Furimazine and also the conventional firefly luciferase/D-luciferin are known to exhibit relatively low tissue permeability and thus less sensitivity for visualization of deep tissue including lungs.

JAK inhibition during the early phase of SARS-CoV-2 infection worsens kidney injury by suppressing endogenous antiviral activity in mice.

Coronavirus disease 2019 (COVID-19) induces respiratory dysfunction as well as kidney injury. Although the kidney is considered a target organ of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and affected by the COVID-19-induced cytokine storm, the mechanisms of renal reaction in SARS-CoV-2 infection are unknown. In this study, a murine COVID-19 model was induced by nasal infection with mouse-adapted SARS-CoV-2 (MA10).

Adjuvant-free parenterally injectable vaccine platform that harnesses previously induced IgG as an antigen delivery carrier.

Subunit vaccines are among the most useful vaccine modalities; however, their low immunogenicity necessitates the addition of adjuvants. Although adjuvants improve immune responses induced by vaccines, they often cause adverse reactions. To address this, we developed an adjuvant-free subunit vaccine platform that uses pre-existing antibodies generated from past infections or vaccinations as carriers for the delivery of vaccine antigens.