Search

Abstract Axis inhibition protein 1 (AXIN1), a scaffold protein interacting with various critical molecules, plays a vital role in determining cell fate. However, its impact on the antiviral innate immune response remains largely unknown. Here, we identify that AXIN1 acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections. In the resting state, AXIN1 maintains the stability of the transcription factor interferon regulatory factor 3 (IRF3) by preventing p62-mediated autophagic degradation of IRF3. This is achieved by recruiting ubiquitin-specific peptidase 35 (USP35), which removes lysine (K) 48-linked ubiquitination at IRF3 K366. Upon virus infection, AXIN1 undergoes a phase separation triggered by phosphorylated TANK-binding kinase 1 (TBK1). This leads to increased phosphorylation of IRF3 and a boost in IFN-I production. Moreover, KYA1797K, a small molecule that binds to the AXIN1 RGS domain, enhances the AXIN1-IRF3 interaction and promotes the elimination of various highly pathogenic viruses. Clinically, patients with HBV-associated hepatocellular carcinoma (HCC) who show reduced AXIN1 expression in pericarcinoma tissues have low overall and disease-free survival rates, as well as higher HBV levels in their blood. Overall, our findings reveal how AXIN1 regulates IRF3 signaling and phase separation-mediated antiviral immune responses, underscoring the potential of the AXIN1 agonist KYA1797K as an effective antiviral agent.

Abstract The persistent COVID-19 pandemic since 2020 has brought an enormous public health burden to the global society and is accompanied by various evolution of the virus genome. The consistently emerging SARS-CoV-2 variants harboring critical mutations impact the molecular characteristics of viral proteins and display heterogeneous behaviors in immune evasion, transmissibility, and the clinical manifestation during infection, which differ each strain and endow them with distinguished features during populational spread. Several SARS-CoV-2 variants, identified as Variants of Concern (VOC) by the World Health Organization, challenged global efforts on COVID-19 control due to the rapid worldwide spread and enhanced immune evasion from current antibodies and vaccines. Moreover, the recent Omicron variant even exacerbated the global anxiety in the continuous pandemic. Its significant evasion from current medical treatment and disease control even highlights the necessity of combinatory investigation of the mutational pattern and influence of the mutations on viral dynamics against populational immunity, which would greatly facilitate drug and vaccine development and benefit the global public health policymaking. Hence in this review, we summarized the molecular characteristics, immune evasion, and impacts of the SARS-CoV-2 variants and focused on the parallel comparison of different variants in mutational profile, transmissibility and tropism alteration, treatment effectiveness, and clinical manifestations, in order to provide a comprehensive landscape for SARS-CoV-2 variant research.

Currently, there are no treatments or vaccines against Epstein-Barr virus (EBV) infection. Here, Zhu et al. isolate gH/gL-specific antibodies from infected donors and identify 1D8, that substantially reduces infection levels in both, B- and epithelial cells, and reduces tumor burdens in EBV-challanged humanized mice due to interferance with the gH/gL-mediated membrane fusion and binding.

Abstract Background Helminths are endemic in more than half of the world’s countries, raising serious public health concerns. Accurate diagnosis of helminth infection is crucial to control strategies. Traditional parasitological methods, serological tests and PCR-based assays are the major means of the diagnosis of helminth infection, but they are time-consuming and/or expensive, and sometimes provide inaccurate results. Loop mediated isothermal amplification (LAMP) assay, a sensitive, simple and rapid method was therefore developed for detection of helminths. This study aims to discuss the current status of application of LAMP on helminths detection and to make a comprehensive evaluation about this updated technology and its future outlook by comparing with several other diagnostic methods. Main body This review summarizes LAMP assay applied for helminth detection and helminthiasis surveillance. The basic principle of LAMP is introduced to help better understand its characteristics and each reported assay is assessed mainly based on its detection sensitivity, specificity and limitations, in comparison with other common diagnostic tests. Moreover, we discuss the limitations of the assays so as to clarify some potential ways of improvement. Conclusions Here, we summarize and discuss the advantages, disadvantages and promising future of LAMP in heliminth detection, which is expected to help update current knowledge and future perspectives of LAMP in highly sensitive and specific diagnosis and surveillance of helminthiasis and other parasitic diseases, and can contribute to the elimination of the diseases from endemic areas.