A novel vesicular stomatitis virus armed with IL-2 mimic for oncolytic therapy.

Oncolytic virus (OV) is increasingly being recognized as a novel vector in cancer immunotherapy. Increasing evidence suggests that OV has the ability to change the immune status of tumor microenvironment, so called transformation of 'cold' tumors into 'hot' tumors. The improved anti-tumor immunity can be induced by OV and further enhanced through the combination of various immunomodulators.

ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating BCL2-BECN1 interaction.

Growing evidences indicate that dysfunction of autophagy contributes to the disease pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two neurodegenerative disorders. The GGGGCC·GGCCCC repeat RNA expansion in chromosome 9 open reading frame 72 () is the most genetic cause of both ALS and FTD. According to the previous studies, GGGGCC·GGCCCC repeat undergoes the unconventional repeat-associated non-ATG translation, which produces dipeptide repeat (DPR) proteins.

SapM hampers host autophagy initiation for intracellular bacillary survival via dephosphorylating Raptor.

Secreted acid phosphatase (SapM) is an immunomodulator of and consequently plays a crucial role in disease onset and development upon infection. Importantly, the virulence of SapM has rendered SapM an attractive target for drug development. However, the mechanism underlying the role of SapM in facilitating bacillary survival remains to be fully elucidated.

Mycobacterial Rv1804c binds to the PEST domain of IκBα and activates macrophage-mediated proinflammatory responses.

Recognition of the components of () by macrophages is vital for initiating a cascade of host immune responses. However, the recognition of -secretory proteins by the receptor-independent pathways of the host remains unclear. Rv1804c is a highly conserved secretory protein in .

Chlorpromazine affects autophagy in association with altered Rag GTPase-mTORC1-TFEB signaling.

Autophagy is a critical protein and organelle quality control system, which regulates cellular homeostasis and survival. Growing pieces of evidence suggest that autophagic dysfunction is strongly associated with many human diseases, including neurological diseases and cancer. Among various autophagic regulators, microphthalmia (MiT)/TFE transcription factors, including transcription factor EB (TFEB), have been shown to act as the master regulators of autophagosome and lysosome biogenesis in both physiological and pathological conditions.

Genome-Wide CRISPR/Cas9 Screening Identifies That Mitochondrial Solute Carrier SLC25A23 Attenuates Type I IFN Antiviral Immunity via Interfering with MAVS Aggregation.

Activation of the mitochondrial antiviral signaling (MAVS) adaptor, also known as IPS-1, VISA, or Cardif, is crucial for antiviral immunity in retinoic acid-inducible gene I (RIG-I)-like receptor signaling. Upon interacting with RIG-I, MAVS undergoes K63-linked polyubiquitination by the E3 ligase Trim31, and subsequently aggregates to activate downstream signaling effectors. However, the molecular mechanisms that modulate MAVS activation are not yet fully understood.

Human OTUD6B positively regulates type I IFN antiviral innate immune responses by deubiquitinating and stabilizing IRF3.

Interferon (IFN) regulatory factor (IRF3) is one of the key factors for type I IFN transcription. To sophisticatedly regulate type I IFN antiviral immune response, IRF3 activity is closely controlled by a variety of post-translational modifications. However, the regulatory mechanisms are still not fully elucidated.

Cardiomyocyte-derived HMGB1 takes a protective role in CVB3-induced viral myocarditis via inhibiting cardiac apoptosis.

Coxsackievirus B3 (CVB3)-induced viral myocarditis (VMC) is characterized by immune cell infiltration and myocardial damage. High mobility group box 1 (HMGB1) is a highly conserved nuclear DNA-binding protein that participates in DNA replication, transcriptional regulation, repair response and inflammatory response in different disease models. To investigate the exact function of HMGB1 in CVB3-induced VMC, we crossed Hmgb1-floxed (Hmgb1 ) mice with mice carrying a suitable Cre recombinase transgenic strain to achieve conditional inactivation of the Hmgb1 gene in a cardiomyocyte-specific manner and to establish myocarditis.

Vesicular stomatitis virus-based vaccine targeting plasmodium blood-stage antigens elicits immune response and protects against malaria with protein booster strategy.

Merozoite invasion of the erythrocytes in humans is a key step in the pathogenesis of malaria. The proteins involved in the merozoite invasion could be potential targets for the development of malaria vaccines. Novel viral-vector-based malaria vaccine regimens developed are currently under clinical trials.

Mycobacterium tuberculosis Rv0790c inhibits the cellular autophagy at its early stage and facilitates mycobacterial survival.

Rv0790c is predicted to be a conserved hypothetical protein encoded by osis (). However, its function in infection remains largely unknown. In this study, we found that Rv0790c promoted bacillary survival of (), both and .

The interaction between E3 ubiquitin ligase Parkin and mitophagy receptor PHB2 links inner mitochondrial membrane ubiquitination to efficient mitophagy.

The autophagic clearance of mitochondria has been defined as mitophagy, which is triggered by mitochondrial damage and serves as a major pathway for mitochondrial homeostasis and cellular quality control. PINK1 and Parkin-mediated mitophagy is the most extensively studied form of mitophagy, which has been linked to the pathogenesis of neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The current paradigm of this particular mitophagy pathway is that the ubiquitination of the outer mitochondrial membrane is the key step to enable the recognition of damaged mitochondria by the core autophagic component autophagosome.

Application of miRNA Biomarkers in Predicting Overall Survival Outcomes for Lung Adenocarcinoma.

Background: With the development of research, the importance of microRNAs (miRNAs) in the occurrence, metastasis, and prognosis of lung adenocarcinoma (LUAD) has attracted extensive attention. This study is aimed at predicting overall survival (OS) results through bioinformatics to identify novel miRNA biomarkers and hub genes.

Materials And Methods: The data of LUAD-related miRNA and mRNA samples was downloaded from The Cancer Genome Atlas (TCGA) database.

A cathelicidin antimicrobial peptide from Hydrophis cyanocinctus inhibits Zika virus infection by downregulating expression of a viral entry factor.

Zika virus (ZIKV) is a re-emerging flavivirus that causes conditions such as microcephaly and testis damage. The spread of ZIKV has become a major public health concern. Recent studies indicated that antimicrobial peptides are an ideal source for screening antiviral candidates with broad-spectrum antiviral activities, including against ZIKV.

Depression compromises antiviral innate immunity via the AVP-AHI1-Tyk2 axis.

Depression is a serious public-health issue. Recent reports have suggested higher susceptibility to viral infections in depressive patients. However, how depression affects antiviral innate immune signaling remains unknown.

A single dose of recombinant VSV-RABV vaccine provides full protection against RABV challenge.

• A replication-competent recombinant VSV with RABV-G protein replacement was generated. • Single dose of VSV-RABV immunization induces potent anti-RABV immune response, including viral neutralizing antibodies. • Mice intranasally immunized with single dose of VSV-RABV were 100% protected upon RABV challenge.

Importin KPNA2 confers HIV-1 pre-integration complex nuclear import by interacting with the capsid protein.

For human immunodeficiency virus 1 (HIV-1) to infect non-dividing cells, pre-integration complex (PIC) must be transported into the nucleus within the replication cycle. We previously reported that the karyopherin β1 (KPNB1)-nucleoporin Pom121 pathway, related to the downstream process of PIC nuclear import, mediates efficient HIV-1 PIC nuclear import. Further, our earlier RNA transcriptome sequencing revealed that karyopherin α2 (KPNA2) was among the differentially expressed importin family members during monocyte to macrophage differentiation.

Identification of miRNA signature for predicting the prognostic biomarker of squamous cell lung carcinoma.

As explorations deepen, the role of microRNAs (miRNAs) in lung squamous cell carcinoma (LUSC), from its emergence to metastasis and prognosis, has elicited extensive concern. LUSC-related miRNA and mRNA samples were acquired from The Cancer Genome Atlas (TCGA) database. The data were initially screened and pretreated, and the R platform and series analytical tools were used to identify the specific and sensitive biomarkers.

Prognostic Implications of Pyroptosis-Related Gene Signatures in Lung Squamous Cell Carcinoma.

Lung squamous cell carcinoma (LUSC) has been a highly malignant tumor with very poor prognosis. It is confirmed that pyroptosis refers to the deaths of cells in a programmed and inflammatory manner. Nevertheless, the correlation between expression of genes related with pyroptosis and their prognosis remains uncertain in LUSC.

Endogenous cathelicidin is required for protection against ZIKV-caused testis damage via inactivating virons.

Cathelicidins have been shown to effectively inhibit flavivirus replication in vitro. However, the effects of mouse and human endogenous cathelicidins on flavivirus infection in vivo are rarely known. We herein found that mouse endogenous cathelicidin CRAMP was significantly up-regulated upon Zika virus (ZIKV) infection.

Targeting matrix metalloproteinase MMP3 greatly enhances oncolytic virus mediated tumor therapy.

In cancer, the extracellular matrix is extensively remodeled during chronic inflammation, thus affecting cell transcription, differentiation, migration and cell-cell interactions. Matrix metalloproteinases can degrade the extracellular matrix of tumor tissues and take important roles in disease progression. Numerous efforts to develop cancer treatments targeting matrix metalloproteinases have failed in clinical trials owing to the ineffectiveness and toxicity of the applied inhibitors.

Cyclovirobuxine D inhibits dengue virus replication by impeding the complete autophagy in a cholesterol-dependent manner.

Dengue virus (DENV) is the most common mosquito-borne flavivirus, and it affects millions of people globally every year. Currently, there are no approved drugs for the treatment of dengue infection. By screening a natural product library, we identified a novel compound, cyclovirobuxine D (Cvb D), that displays anti-DENV activity.

Ubiquitin E3 Ligase c-Cbl Is a Host Negative Regulator of Nef Protein of HIV-1.

Nef is an accessory protein encoded by human immunodeficiency virus type-1 (HIV-1) and plays important roles in regulating HIV-1 infection and viral replication. Interestingly, HIV-1 Nef can promote degradation of numerous host proteins to disrupt cellular antiviral immune response. However, how HIV-1 Nef is degraded by host factors remains largely unexplored.

Mycobacterium tuberculosis MmsA (Rv0753c) Interacts with STING and Blunts the Type I Interferon Response.

Type I interferon (IFN) plays an important role in persistence and disease pathogenesis. has evolved a number of mechanisms to evade host immune surveillance. However, it is unclear how the type I IFN response is tightly regulated by the determinants.

USP39 Serves as a Deubiquitinase to Stabilize STAT1 and Sustains Type I IFN-Induced Antiviral Immunity.

Deubiquitinating enzymes (DUBs) are cysteine proteases that reverse the ubiquitination by removing ubiquitins from the target protein. The human genome encodes ∼100 potential DUBs, which can be classified into six families, influencing multiple cellular processes, such as antiviral responses, inflammatory responses, apoptosis, etc. To systematically explore the role of DUBs involved in antiviral immunity, we performed an RNA interference-based screening that contains 97 human DUBs.

Mycobacterium tuberculosis Rv1096, facilitates mycobacterial survival by modulating the NF-κB/MAPK pathway as peptidoglycan N-deacetylase.

Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that can infect and replicate in macrophages. Peptidoglycan (PGN) is a major component of the mycobacterial cell wall and is recognized by host pattern recognition receptors (PRRs). Many bacteria modulate and evade the immune defenses of their hosts through PGN deacetylation.