Background: DNA damage response and miRNAs have been linked to cancer progression. Results: Genotoxic drug induces up-regulation of miR-21 in a NF-B-and STAT3-dependent manner, which correlates with enhanced breast cancer cell invasion. Conclusion: Genotoxic NF-B activation promotes breast cancer invasion via miR-21 induction. Significance: Genotoxic NF-B signaling pathway may serve as a drug target to reduce therapeutic resistance and metastasis in breast cancer.

Dectin-1 signalling in dendritic cells (DCs) has an important role in triggering protective antifungal Th17 responses. However, whether dectin-1 directs DCs to prime antitumour Th9 cells remains unclear. Here, we show that DCs activated by dectin-1 agonists potently promote naive CD4+ T cells to differentiate into Th9 cells. Abrogation of dectin-1 in DCs completely abolishes their Th9-polarizing capability in response to dectin-1 agonist curdlan. Notably, dectin-1 stimulation of DCs upregulates TNFSF15 and OX40L, which are essential for dectin-1-activated DC-induced Th9 cell priming. Mechanistically, dectin-1 activates Syk, Raf1 and NF-κB signalling pathways, resulting in increased p50 and RelB nuclear translocation and TNFSF15 and OX40L expression. Furthermore, immunization of tumour-bearing mice with dectin-1-activated DCs induces potent antitumour response that depends on Th9 cells and IL-9 induced by dectin-1-activated DCs in vivo. Our results identify dectin-1-activated DCs as a powerful inducer of Th9 cells and antitumour immunity and may have important clinical implications.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen of current COVID-19 pandemic, and insufficient production of type I interferon (IFN-I) is associated with the severe forms of the disease. Membrane (M) protein of SARS-CoV-2 has been reported to suppress host IFN-I production, but the underlying mechanism is not completely understood. In this study, SARS-CoV-2 M protein was confirmed to suppress the expression of IFNβ and interferon-stimulated genes induced by RIG-I, MDA5, IKKϵ, and TBK1, and to inhibit IRF3 phosphorylation and dimerization caused by TBK1. SARS-CoV-2 M could interact with MDA5, TRAF3, IKKϵ, and TBK1, and induce TBK1 degradation via K48-linked ubiquitination. The reduced TBK1 further impaired the formation of TRAF3–TANK–TBK1-IKKε complex that leads to inhibition of IFN-I production. Our study revealed a novel mechanism of SARS-CoV-2 M for negative regulation of IFN-I production, which would provide deeper insight into the innate immunosuppression and pathogenicity of SARS-CoV-2.

The recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of ongoing global pandemic of COVID-19, may trigger immunosuppression in the early stage and overactive immune response in the late stage of infection; However, the underlying mechanisms are not well understood. Here we demonstrated that the SARS-CoV-2 nucleocapsid (N) protein dually regulated innate immune responses, i.e., the low-dose N protein suppressed type I interferon (IFN-I) signaling and inflammatory cytokines, whereas high-dose N protein promoted IFN-I signaling and inflammatory cytokines. Mechanistically, the SARS-CoV-2 N protein dually regulated the phosphorylation and nuclear translocation of IRF3, STAT1, and STAT2. Additionally, low-dose N protein combined with TRIM25 could suppress the ubiquitination and activation of retinoic acid-inducible gene I (RIG-I). Our findings revealed a regulatory mechanism of innate immune responses by the SARS-CoV-2 N protein, which would contribute to understanding the pathogenesis of SARS-CoV-2 and other SARS-like coronaviruses, and development of more effective strategies for controlling COVID-19.

Chronic hepatitis B virus (HBV) infection imposes a severe burden on global public health. Currently, there are no curative therapies for millions of chronic HBV-infected patients (Lok et al., 2017). Interferon (IFN; including pegylated IFN) is an approved anti-HBV drug that not only exerts direct antiviral activity, but also augments immunity against HBV infection. Through a systematic review of the literature, here we summarize and present recent progress in research regarding the interactions between IFN and HBV as well as dissect the antiviral mechanisms of IFN. We focus on inhibition of HBV replication by IFN-stimulated genes (ISGs) as well as inhibition of IFN signaling by HBV and viral proteins. Finally, we briefly discuss current IFN-based HBV treatment strategies. This review may help to better understand the mechanisms involved in the therapeutic action of IFN as well as the crosstalk between IFN and HBV, and facilitate the development of both direct-acting and immunology-based new HBV drugs.

To examine the prevalence of HIV, syphilis, and hepatitis C virus (HCV) infections by demographic characteristics and identify the subgroups of female sex workers (FSW) who are at a higher risk of the infections. Secondary analysis of the 2010 National Sentinel Surveillance (NSS) data was conducted in the current study. A total of 12,622 FSW recruited from 35 NSS sites in Guangxi, China were included in the analysis. FSW were tested for HIV, syphilis, and HCV. The overall prevalence of HIV, syphilis, and HCV infections were 1.0%, 6.1% and 1.0%, respectively. The prevalence of HIV and syphilis infections were significantly higher among women who aged 40 years or older, worked in small commercial sex venues or on street, divorced or widowed, or no formal schooling. A very high HIV infection prevalence (8.2%) was observed among a small number of cross-border foreign FSW (n=49). The prevalence of HCV infection did not differ by most of the demographic characteristics. Living in other provinces or being a Zhuang-ethnic served as protective factors for HCV. The multivariable analyses confirmed the results of bivariate results suggesting higher prevalence of HIV and syphilis infections among FSW who were older, divorced or widowed, or no formal schooling. Future HIV intervention prevention efforts among FSW need to pay particular attention to these women in order to effectively curtail the infections among this most-at-risk population as well as to prevent the further spread of HIV and syphilis to other populations.

Background: UV radiation-induced miRNA expression modulates cellular stress response. Results: UV up-regulates miR-125b expression via ATM-dependent NF-B activation, which represses p38␣ expression. Conclusion: UV-induced miR-125b prevents prolonged p38␣ activation and thereby promotes cell survival. Significance: Up-regulation of miR-125b serves as a negative feedback mechanism to control p38␣ activity upon UV radiation, which may contribute to tumorigenesis of skin cancer.

To understand the molecular mechanisms that mediate the anti-hepatitis B virus (HBV) effect of interferon (IFN) therapy, we conduct highthroughput bimolecular fluorescence complementation screening to identify potential physical interactions between the HBx protein and 145 IFNstimulated genes (ISGs). Seven HBx-interacting ISGs have consistent and significant inhibitory effects on HBV replication, among which TRIM5g suppresses HBV replication by promoting K48-linked ubiquitination and degradation of the HBx protein on the K95 ubiquitin site. The B-Box domain of TRIM5g under overexpression conditions is sufficient to trigger HBx degradation and is responsible both for interacting with HBx and recruiting TRIM31, which is an ubiquitin ligase that triggers HBx ubiquitination. High expression levels of TRIM5g in IFN-a-treated HBV patients might indicate a better therapeutic effect. Thus, our studies identify a crucial role for TRIM5g and TRIM31 in promoting HBx degradation, which may facilitate the development of therapeutic agents for the treatment of patients with IFN-resistant HBV infection.