Epigenetic repression of antiviral genes by SARS-CoV-2 NSP1.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades the innate immune machinery through multiple viral proteins, including nonstructural protein 1 (NSP1). While NSP1 is known to suppress translation of host mRNAs, the mechanisms underlying its immune evasion properties remain elusive. By integrating RNA-seq, ribosome footprinting, and ChIP-seq in A549 cells we found that NSP1 predominantly represses transcription of immune-related genes by favoring Histone 3 Lysine 9 dimethylation (H3K9me2).

Beta-coronaviruses exploit cellular stress responses by modulating TFEB and TFE3 activity.

Beta-coronaviruses have emerged as a severe threat to global health. Undercovering the interplay between host and beta-coronaviruses is essential for understanding disease pathogenesis and developing efficient treatments. Here we report that the transcription factors TFEB and TFE3 translocate from the cytosol to the nucleus in response to beta-coronavirus infection by a mechanism that requires activation of calcineurin phosphatase.

Membrane-assisted assembly and selective secretory autophagy of enteroviruses.

Enteroviruses are non-enveloped positive-sense RNA viruses that cause diverse diseases in humans. Their rapid multiplication depends on remodeling of cytoplasmic membranes for viral genome replication. It is unknown how virions assemble around these newly synthesized genomes and how they are then loaded into autophagic membranes for release through secretory autophagy.

Vesicle-Cloaked Rotavirus Clusters are Environmentally Persistent and Resistant to Free Chlorine Disinfection.

Recent discovery of vesicle-cloaked virus clusters (i.e., viral vesicles) has greatly challenged the central paradigm of viral transmission and infection as a single virion.

Waterborne Human Pathogenic Viruses in Complex Microbial Communities: Environmental Implication on Virus Infectivity, Persistence, and Disinfection.

Waterborne human pathogenic viruses challenge global health and economy. Viruses were long believed to transmit among hosts as individual, free particles. However, recent evidence indicates that viruses also transmit in populations, so-called en bloc transmission, by either interacting with coexisting bacteria, free-living amoebas, and other higher organisms through endosymbiosis and surface binding, or by being clustered inside membrane-bound vesicles or simply self-aggregating with themselves.

A New Infectious Unit: Extracellular Vesicles Carrying Virus Populations.

Viral egress and transmission have long been described to take place through single free virus particles. However, viruses can also shed into the environment and transmit as populations clustered inside extracellular vesicles (EVs), a process we had first called vesicle-mediated en bloc transmission. These membrane-cloaked virus clusters can originate from a variety of cellular organelles including autophagosomes, plasma membrane, and multivesicular bodies.

Enrichment of NPC1-deficient cells with the lipid LBPA stimulates autophagy, improves lysosomal function, and reduces cholesterol storage.

Niemann-Pick C (NPC) is an autosomal recessive disorder characterized by mutations in the NPC1 or NPC2 genes encoding endolysosomal lipid transport proteins, leading to cholesterol accumulation and autophagy dysfunction. We have previously shown that enrichment of NPC1-deficient cells with the anionic lipid lysobisphosphatidic acid (LBPA; also called bis(monoacylglycerol)phosphate) via treatment with its precursor phosphatidylglycerol (PG) results in a dramatic decrease in cholesterol storage. However, the mechanisms underlying this reduction are unknown.

Viral pores are everywhere.

Jones et al. (2021) and Zhang et al. (2021) reveal by cryo-EM the oligomeric crown-like structure formed by a membrane-associated Chikungunya virus replication protein that gates the export of newly synthesized viral RNA from viral replication organelles.

Emerging Pathogenic Unit of Vesicle-Cloaked Murine Norovirus Clusters is Resistant to Environmental Stresses and UV Disinfection.

An individual virion was long believed to act as an independent infectious unit in virology, until the recent discovery of vesicle-cloaked virus clusters which has greatly challenged this central paradigm. Vesicle-cloaked virus clusters (also known as viral vesicles) are phospholipid-bilayer encapsulated fluid sacs that contain multiple virions or multiple copies of viral genomes. Norovirus is a global leading causative agent of gastroenteritis, and the reported prevalence of vesicle-cloaked norovirus clusters in stool has raised concerns whether the current disinfection, sanitation, and hygiene practices can effectively control environmental pollution by these pathogenic units.

Luminal microvesicles uniquely influence translocating bacteria after SIV infection.

Microbial translocation contributes to persistent inflammation in both treated and untreated HIV infection. Although translocation is due in part to a disintegration of the intestinal epithelial barrier, there is a bias towards the translocation of Proteobacteria. We hypothesized that intestinal epithelial microvesicle cargo differs after HIV infection and contributes to biased translocation.

β-Coronaviruses Use Lysosomes for Egress Instead of the Biosynthetic Secretory Pathway.

β-Coronaviruses are a family of positive-strand enveloped RNA viruses that includes the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much is known regarding their cellular entry and replication pathways, but their mode of egress remains uncertain. Using imaging methodologies and virus-specific reporters, we demonstrate that β-coronaviruses utilize lysosomal trafficking for egress rather than the biosynthetic secretory pathway more commonly used by other enveloped viruses.

Norovirus infection causes acute self-resolving diarrhea in wild-type neonatal mice.

Human noroviruses are the leading cause of severe childhood diarrhea worldwide, yet we know little about their pathogenic mechanisms. Murine noroviruses cause diarrhea in interferon-deficient adult mice but these hosts also develop systemic pathology and lethality, reducing confidence in the translatability of findings to human norovirus disease. Herein we report that a murine norovirus causes self-resolving diarrhea in the absence of systemic disease in wild-type neonatal mice, thus mirroring the key features of human norovirus disease and representing a norovirus small animal disease model in wild-type mice.

Constitutive Activation of the B Cell Receptor Underlies Dysfunctional Signaling in Chronic Lymphocytic Leukemia.

In cancer biology, the functional interpretation of genomic alterations is critical to achieve the promise of genomic profiling in the clinic. For chronic lymphocytic leukemia (CLL), a heterogeneous disease of B-lymphocytes maturing under constitutive B cell receptor (BCR) stimulation, the functional role of diverse clonal mutations remains largely unknown. Here, we demonstrate that alterations in BCR signaling dynamics underlie the progression of B cells toward malignancy.

Insane in the Membrane: Glial Extracellular Vesicles Transmit Polyomaviruses.

Extracellular vesicles (EVs) are major vehicles for transporting viruses among hosts. While RNA viruses make up the great majority of transmission by EVs, in a recent article in (mBio 10:e00379-19, 2019, https://mbio.asm.

Extracellular vesicles: Vehicles of en bloc viral transmission.

En Bloc transmission of viruses allow multiple genomes to collectivelly penetrate and initiate infection in the same cell, often resulting in enhanced infectivity. Given the quasispecies (mutant cloud) nature of RNA viruses and many DNA viruses, en bloc transmission of multiple genomes provides different starting points in sequence space to initiate adaptive walks, and has implications for modulation of viral fitness and for the response of viral populations to lethal mutagenesis. Mechanisms that can enable multiple viral genomes to be transported en bloc among hosts has only recently been gaining attention.

Vesicle-Cloaked Virus Clusters Are Optimal Units for Inter-organismal Viral Transmission.

In enteric viral infections, such as those with rotavirus and norovirus, individual viral particles shed in stool are considered the optimal units of fecal-oral transmission. We reveal that rotaviruses and noroviruses are also shed in stool as viral clusters enclosed within vesicles that deliver a high inoculum to the receiving host. Cultured cells non-lytically release rotaviruses and noroviruses inside extracellular vesicles.

Enterovirus Transmission by Secretory Autophagy.

Present in many cell types, non-degradative secretory autophagy is a newly discovered pathway in which autophagosomes fuse with the plasma membrane instead of lysosomes. Surprisingly, some viruses exploit secretory autophagy to exit cells non-lytically, shedding into the extracellular environment as particle populations contained within vesicles. As a result, this significantly enhances the infectivity of these viruses.

Infection with hepatitis C virus depends on TACSTD2, a regulator of claudin-1 and occludin highly downregulated in hepatocellular carcinoma.

Entry of hepatitis C virus (HCV) into hepatocytes is a complex process that involves numerous cellular factors, including the scavenger receptor class B type 1 (SR-B1), the tetraspanin CD81, and the tight junction (TJ) proteins claudin-1 (CLDN1) and occludin (OCLN). Despite expression of all known HCV-entry factors, in vitro models based on hepatoma cell lines do not fully reproduce the in vivo susceptibility of liver cells to primary HCV isolates, implying the existence of additional host factors which are critical for HCV entry and/or replication. Likewise, HCV replication is severely impaired within hepatocellular carcinoma (HCC) tissue in vivo, but the mechanisms responsible for this restriction are presently unknown.

Catch and Release of Cytokines Mediated by Tumor Phosphatidylserine Converts Transient Exposure into Long-Lived Inflammation.

Immune cells constantly survey the host for pathogens or tumors and secrete cytokines to alert surrounding cells of these threats. In vivo, activated immune cells secrete cytokines for several hours, yet an acute immune reaction occurs over days. Given these divergent timescales, we addressed how cytokine-responsive cells translate brief cytokine exposure into phenotypic changes that persist over long timescales.

Correction: Influenza A Virus Assembly Intermediates Fuse in the Cytoplasm.

[This corrects the article DOI: 10.1371/journal.ppat.

Lipid Tales of Viral Replication and Transmission.

Positive-strand RNA viruses are the largest group of RNA viruses on Earth and cellular membranes are critical for all aspects of their life cycle, from entry and replication to exit. In particular, membranes serve as platforms for replication and as carriers to transmit these viruses to other cells, the latter either as an envelope surrounding a single virus or as the vesicle containing a population of viruses. Notably, many animal and human viruses appear to induce and exploit phosphatidylinositol 4-phosphate/cholesterol-enriched membranes for replication, whereas many plant and insect-vectored animal viruses utilize phosphatidylethanolamine/cholesterol-enriched membranes for the same purpose; and phosphatidylserine-enriched membrane carriers are widely used by both single and populations of viruses for transmission.

Cloud storage for endosomes.

Coordinated regulation of vesicle trafficking is critical for the proper functioning of a cell. The bulk of cellular transport vesicles are sequestered in a “perinuclear cloud”, with only a small fraction released to the cell periphery. Jongsma (2016) found that the ER‐associated E3 ubiquitin ligase RNF26 is responsible for establishing and maintaining the architecture of the perinuclear cloud and that this spatiotemporal positioning is critical for effective regulation of the endocytic and exocytic systems.