SARS-CoV-2 NSP3/4 control formation of replication organelle and recruitment of RNA polymerase NSP12.

β-coronavirus rearranges the host cellular membranes to form double-membrane vesicles (DMVs) via NSP3/4, which anchor replication-transcription complexes (RTCs), thereby constituting the replication organelles (ROs). However, the impact of specific domains within NSP3/4 on DMV formation and RO assembly remains largely unknown. By using cryogenic-correlated light and electron microscopy (cryo-CLEM), we discovered that the N-terminal and C-terminal domains (NTD and CTD) of SARS-CoV-2 NSP3 are essential for DMV formation.

Cytoskeletal Vimentin Directs Cell-Cell Transmission of Hepatitis C Virus.

Hepatitis C virus (HCV) is a major human pathogen causing liver diseases. Although direct-acting antiviral agents effectively inhibit HCV infection, cell-cell transmission remains a critical venue for HCV persistence in vivo. However, the underlying mechanism of how HCV spreads intercellularly remains elusive.

Gut commensal bacteria Parabacteroides goldsteinii-derived outer membrane vesicles suppress skin inflammation in psoriasis.

Despite gut microbiota-derived extracellular vesicles (EVs) serving as pivotal mediators in bacteria-host cell interactions, their potential role in modulating skin inflammation remains poorly understood. Here, we developed strategies for mass production of Parabacteroides goldsteinii-derived outer membrane vesicles (Pg OMVs), commonly known as EVs. We found that orally administered Pg OMVs can reach the colon, traverse the intestinal barrier, and circulate to the inflamed skin of psoriasis-like mice, resulting in reduced epidermal hyperplasia, suppressed infiltration of inflammatory cells in the skin lesions, and effective amelioration of both skin and systemic inflammation.

Host caveolin-1 facilitates Zika virus infection by promoting viral RNA replication.

Zika virus (ZIKV) has gained notoriety in recent years because there are no targeted therapies or vaccines available so far. Caveolin-1 (Cav-1) in host cells plays crucial functions in the invasion of many viruses. However, its specific involvement in ZIKV infection has remained unclear.

Discovery of Trametinib as an orchestrator for cytoskeletal vimentin remodeling.

The dynamic remodeling of the cytoskeletal network of vimentin intermediate filaments supports various cellular functions, including cell morphology, elasticity, migration, organelle localization, and resistance against mechanical or pathological stress. Currently available chemicals targeting vimentin predominantly induce network reorganization and shrinkage around the nucleus. Effective tools for long-term manipulation of vimentin network dispersion in living cells are still lacking, limiting in-depth studies on vimentin function and potential therapeutic applications.

ATG14 targets lipid droplets and acts as an autophagic receptor for syntaxin18-regulated lipid droplet turnover.

Lipid droplets (LDs) are dynamic lipid storage organelles that can be degraded by autophagy machinery to release neutral lipids, a process called lipophagy. However, specific receptors and regulation mechanisms for lipophagy remain largely unknown. Here, we identify that ATG14, the core unit of the PI3KC3-C1 complex, also targets LD and acts as an autophagic receptor that facilitates LD degradation.

Vimentin cage - A double-edged sword in host anti-infection defense.

Vimentin, a type III intermediate filament, reorganizes into what is termed the 'vimentin cage' in response to various pathogenic infections. This cage-like structure provides an envelope to key components of the pathogen's life cycle. In viral infections, the vimentin cage primarily serves as a scaffold and organizer for the replication factory, promoting viral replication.

Coronavirus and the Cytoskeleton of Virus-Infected Cells.

The cytoskeleton, which includes actin filaments, microtubules, and intermediate filaments, is one of the most important networks in the cell and undertakes many fundamental life activities. Among them, actin filaments are mainly responsible for maintaining cell shape and mediating cell movement, microtubules are in charge of coordinating all cargo transport within the cell, and intermediate filaments are mainly thought to guard against external mechanical pressure. In addition to this, cytoskeleton networks are also found to play an essential role in multiple viral infections.

NDP52 mediates an antiviral response to hepatitis B virus infection through Rab9-dependent lysosomal degradation pathway.

Autophagy receptor NDP52 triggers bacterial autophagy against infection. However, the ability of NDP52 to protect against viral infection has not been established. We show that NDP52 binds to envelope proteins of hepatitis B virus (HBV) and triggers a degradation process that promotes HBV clearance.

Quantitatively mapping local quality of super-resolution microscopy by rolling Fourier ring correlation.

In fluorescence microscopy, computational algorithms have been developed to suppress noise, enhance contrast, and even enable super-resolution (SR). However, the local quality of the images may vary on multiple scales, and these differences can lead to misconceptions. Current mapping methods fail to finely estimate the local quality, challenging to associate the SR scale content.

Single particle tracking reveals SARS-CoV-2 regulating and utilizing dynamic filopodia for viral invasion.

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry mechanism has been explored, little is known about how SARS-CoV-2 regulates the subcellular structural remodeling to invade multiple organs and cell types. Here, we unveil how SARS-CoV-2 boosts and utilizes filopodia to enter the target cells by real-time imaging. Using SARS-CoV-2 single virus-like particle (VLP) tracking in live cells and sparse deconvolution algorithm, we uncover that VLPs utilize filopodia to reach the entry site in two patterns, "surfing" and "grabbing", which avoid the virus from randomly searching on the plasma membrane.

Actomyosin-dependent cell contractility orchestrates Zika virus infection.

Emerging pathogen infections, such as Zika virus (ZIKV), pose an increasing threat to human health, but the role of mechanobiological attributes of host cells during ZIKV infection is largely unknown. Here, we reveal that ZIKV infection leads to increased contractility of host cells. Importantly, we investigated whether host cell contractility contributes to ZIKV infection efficacy, from both the intracellular and extracellular perspective.

Vaccinia virus induces EMT-like transformation and RhoA-mediated mesenchymal migration.

The emerging outbreak of monkeypox is closely associated with the viral infection and spreading, threatening global public health. Virus-induced cell migration facilitates viral transmission. However, the mechanism underlying this type of cell migration remains unclear.

Discovery of a fused bicyclic derivative of 4-hydroxypyrrolidine and imidazolidinone as a new anti-HCV agent.

Hepatitis C virus (HCV) infection causes severe liver diseases and remains a major global public health concern. Current direct-acting antiviral (DAA)-based therapies that target viral proteins involving HCV genome replication are effective, however a minority of patients still fail to cure HCV, rendering a window to develop additional antivirals particularly targeting host functions involving in HCV infection. Here, we utilized the HCV infection cell culture system (HCVcc) to screen in-house compounds bearing host-interacting preferred scaffold for the antiviral activity.

Lamin A/C and Vimentin as a Coordinated Regulator during Amoeboid Migration in Microscale Confined Microenvironments.

Cell migration occurs in confined microenvironments, which plays a vital role in the process of tumor metastasis. However, it is challenging to study their behaviors in vivo. Here we developed a cell squeeze system that can be scaled down to micrometers to mimic native physical confined microenvironments, wherein degrees of surface adhesion and mechanical constraints could be manipulated in order to investigate cell-migrating behaviors.

The global epidemic trend analysis of influenza type B drug resistance sites from 2006 to 2018.

Introduction: Influenza is a severe respiratory viral infection that causes significant morbidity and mortality, due to annual epidemics and unpredictable pandemics. With the extensive use of neuraminidase inhibitor (NAI) drugs, the influenza B virus has carried different drug-resistant mutations. Thus, this study aimed to analyze the prevalence of drug-resistant mutations of the influenza B virus.

Cytoskeleton network participates in the anti-infection responses of macrophage.

During immune responses against invading pathogenic bacteria, the cytoskeleton network enables macrophages to implement multiple essential functions. To protect the host from infection, macrophages initially polarize to adopt different phenotypes in response to distinct signals from the microenvironment. The extracellular stimulus regulates the rearrangement of the cytoskeleton, thereby altering the morphology and migratory properties of macrophages.

Coronaviral ORF6 protein mediates inter-organelle contacts and modulates host cell lipid flux for virus production.

Lipid droplets (LDs) form inter-organelle contacts with the endoplasmic reticulum (ER) that promote their biogenesis, while LD contacts with mitochondria enhance β-oxidation of contained fatty acids. Viruses have been shown to take advantage of lipid droplets to promote viral production, but it remains unclear whether they also modulate the interactions between LDs and other organelles. Here, we showed that coronavirus ORF6 protein targets LDs and is localized to the mitochondria-LD and ER-LD contact sites, where it regulates LD biogenesis and lipolysis.

Salmonella effector SopB reorganizes cytoskeletal vimentin to maintain replication vacuoles for efficient infection.

A variety of intracellular bacteria modulate the host cytoskeleton to establish subcellular niches for replication. However, the role of intermediate filaments, which are crucial for mechanical strength and resilience of the cell, and in bacterial vacuole preservation remains unclear. Here, we show that Salmonella effector SopB reorganizes the vimentin network to form cage-like structures that surround Salmonella-containing vacuoles (SCVs).

The diverse actions of cytoskeletal vimentin in bacterial infection and host defense.

Bacterial infection is a major threat to human health, with infections resulting in considerable mortality, urging the need for a more profound understanding of bacteria-host interactions. During infection of cells, host cytoskeletal networks constantly interact with bacteria and are integral to their uptake. Vimentin, an intermediate filament protein, is one such cytoskeletal component that interacts with bacteria during infection.

Vimentin Suppresses Inflammation and Tumorigenesis in the Mouse Intestine.

Vimentin has been implicated in wound healing, inflammation, and cancer, but its functional contribution to intestinal diseases is poorly understood. To study how vimentin is involved during tissue injury and repair of simple epithelium, we induced colonic epithelial cell damage in the vimentin null (Vim) mouse model. Vim mice challenged with dextran sodium sulfate (DSS) had worse colitis manifestations than wild-type (WT) mice.

Host cytoskeletal vimentin serves as a structural organizer and an RNA-binding protein regulator to facilitate Zika viral replication.

Emerging microbe infections, such as Zika virus (ZIKV), pose an increasing threat to human health. Investigations on ZIKV replication have revealed the construction of replication complexes (RCs), but the role of cytoskeleton in this process is largely unknown. Here, we investigated the function of cytoskeletal intermediate filament protein vimentin in the life cycle of ZIKV infection.

Cell migration orchestrates migrasome formation by shaping retraction fibers.

Migrasomes are recently discovered vesicle-like structures on retraction fibers of migrating cells that have been linked with transfer of cellular contents, shedding of unwanted materials, and information integration. However, whether and how the cell migration paradigm regulates migrasome formation is not clear. Here, we report that there are significantly fewer migrasomes in turning cells compared with straight persistently migrating cells.

How Physical Factors Coordinate Virus Infection: A Perspective From Mechanobiology.

Pandemics caused by viruses have threatened lives of thousands of people. Understanding the complicated process of viral infection provides significantly directive implication to epidemic prevention and control. Viral infection is a complex and diverse process, and substantial studies have been complemented in exploring the biochemical and molecular interactions between viruses and hosts.