Autophagy is a catabolic process by which cells remove long-lived proteins and damaged organelles for recycling. Viral infections may also induce autophagic response. Here we show that hepatitis B virus (HBV), a pathogen that chronically infects ≈350 million people globally, can enhance autophagic response in cell cultures, mouse liver, and during natural infection. This enhancement of the autophagic response is not coupled by an increase of autophagic protein degradation and is dependent on the viral X protein, which binds to and enhances the enzymatic activity of phosphatidylinositol 3-kinase class III, an enzyme critical for the initiation of autophagy. Further analysis indicates that autophagy enhances HBV DNA replication, with minimal involvement of late autophagic vacuoles in this process. Our studies thus demonstrate that a DNA virus can use autophagy to enhance its own replication and indicate the possibility of targeting the autophagic pathway for the treatment of HBV patients.autophagy | hepatitis B virus DNA replication | hepatitis B virus X protein | PI3KC3A utophagy is a catabolic process by which long-lived proteins and damaged organelles are sequestered in the cytoplasm and removed for recycling. It is important for maintaining cellular homeostasis. During autophagy, membrane crescents appear in the cytoplasm. These membranes will eventually form a double-membrane structure known as autophagosomes, which will mature by fusing with lysosomes to form autolysosomes. The contents of autophagosomes will subsequently be degraded by lysosomal enzymes. Autophagy has also been implicated in innate and adaptive immune responses to the infection of microbial pathogens (1, 2). A number of viruses have been shown to induce autophagy, either completely or partially, and often with either a destructive or beneficial result to themselves. For examples, several single-stranded RNA viruses such as poliovirus, coronavirus, dengue virus, and hepatitis C virus all seem to induce the accumulation of autophagic vacuoles and use these membrane vesicles to benefit their replication (3-6). In contrast, other viruses such as herpes simplex virus-1 (HSV-1), cytomegalovirus (CMV), and Kaposi's sarcoma herpes virus (KSHV) have evolved mechanisms to suppress autophagy and, in the case of HSV-1, for its own survival (2).Hepatitis B virus (HBV) belongs to the Hepadnavirus family. This virus has a 3.2-kb circular and partially double-stranded DNA genome that contains four genes named S, C, P, and X genes. The S gene codes for the surface antigens (i.e., envelope proteins), the C gene codes for the core protein and a related protein termed precore protein, the P gene codes for the viral DNA polymerase, and the X gene codes for a multifunctional regulatory protein. After its synthesis, the core protein packages its own mRNA, which is also known as the pregenomic RNA (pgRNA), to form the core particle. The pgRNA will be converted to the DNA genome in the core particle by the viral DNA polymerase, which is also a reverse transcriptase...

Despite evidence from a number of Earth systems that abrupt temporal changes known as regime shifts are important, their nature, scale and mechanisms remain poorly documented and understood. Applying principal component analysis, change‐point analysis and a sequential t‐test analysis of regime shifts to 72 time series, we confirm that the 1980s regime shift represented a major change in the Earth's biophysical systems from the upper atmosphere to the depths of the ocean and from the Arctic to the Antarctic, and occurred at slightly different times around the world. Using historical climate model simulations from the Coupled Model Intercomparison Project Phase 5 (CMIP5) and statistical modelling of historical temperatures, we then demonstrate that this event was triggered by rapid global warming from anthropogenic plus natural forcing, the latter associated with the recovery from the El Chichón volcanic eruption. The shift in temperature that occurred at this time is hypothesized as the main forcing for a cascade of abrupt environmental changes. Within the context of the last century or more, the 1980s event was unique in terms of its global scope and scale; our observed consequences imply that if unavoidable natural events such as major volcanic eruptions interact with anthropogenic warming unforeseen multiplier effects may occur.

Background: Hepatitis C virus (HCV) induces autophagosomes in its host cells. Results: The HCV RNA replication complex colocalizes with autophagosomes, which are induced by HCV via a Class III PI3K-independent pathway. Conclusion: HCV induces autophagosomes and uses their membranes for its RNA replication. Significance: The perturbation of the autophagic pathway by HCV may have important consequences in HCV pathogenesis.

Artículo de publicación ISISome 290 species of squids comprise the order Teuthida that belongs to the molluscan Class Cephalopoda. Of these, about 30-40 squid species have substantial commercial importance around the world. Squid fisheries make a rather small contribution to world landings from capture fisheries relative to that of fish, but the proportion has increased steadily over the last decade, with some signs of recent leveling off. The present overview describes all substantial squid fisheries around the globe. The main ecological and biological features of exploited stocks, and key aspects of fisheries management are presented for each commercial species of squid worldwide. The history and fishing methods used in squid fisheries are also described. Special attention has been paid to interactions between squid fisheries and marine ecosystems including the effects of fishing gear, the role of squid in ecosystem change induced by overfishing on groundfish, and ecosystem-based fishery management

Summary Autophagy is required for benign hepatic tumors to progress into malignant hepatocellular carcinoma. However, the mechanism is unclear. Here we report that mitophagy, the selective removal of mitochondria by autophagy, positively regulates hepatic cancer stem cells (CSCs) by suppressing the tumor suppressor p53. When mitophagy is enhanced, p53 colocalizes with mitochondria and is removed by a mitophagy-dependent manner. However, when mitophagy is inhibited, p53 is phosphorylated at serine-392 by PINK1, a kinase associated with mitophagy, on mitochondria and translocated into the nucleus where it binds to the NANOG promoter to prevent OCT4 and SOX2 transcription factors from activating the expression of NANOG, a transcription factor critical for maintaining the stemness and the self-renewal ability of CSCs, resulting in the reduction of hepatic CSC populations. These results demonstrate that mitophagy controls the activities of p53 to maintain hepatic CSCs and provide an explanation to why autophagy is required to promote hepatocarcinogenesis.

Hepatitis B virus (HBV) is a hepatotropic virus that can cause severe liver diseases, including liver cirrhosis and hepatocellular carcinoma. This virus chronically infects approximately 350 million people in the world, causing significant morbidity and mortality. HBV is a small DNA virus with a partially double-stranded and circular DNA genome that has a length of about 3.2 kb. After the infection of hepatocytes, this DNA is repaired to form a covalently closed circular DNA (cccDNA) molecule, which then directs the transcription of viral mRNAs. The mRNA of the viral core protein is larger than the genome length. This core protein mRNA, which is also termed the pregenomic RNA (pgRNA), is packaged by the core protein to form the viral core particle. It is subsequently converted to the partially double-stranded viral genome by the viral RNA polymerase, which is also packaged in the core particle. The core particle subsequently interacts with the viral envelope proteins for the formation of the mature virion, which is then released from infected cells (for a review, see reference 1).Recently, we demonstrated that HBV can induce autophagy in cell cultures, in the mouse liver, and during natural infection

Summary In contrast to horizontal transmission of hepatitis B virus (HBV) between adults, which often leads to self-limited acute infection, vertical transmission of HBV from mother to child often leads to chronic infection. However, the mechanisms linking vertical transmission with chronic infection are not known. We developed a mouse model to study the effect of maternal HBV infection on HBV persistence in offspring and found that HBV carried by the mother impaired CD8+ T cell responses to HBV in her offspring, resulting in HBV persistence. This impairment of CD8+ T cell responses was mediated by hepatic macrophages, which were predisposed by maternal HBV e antigen (HBeAg) to support HBV persistence by upregulation of inhibitory ligand PD-L1 and altered polarization upon restimulation with HBeAg. Depletion of hepatic macrophages led to CD8+ T cell activation and HBV clearance in the offspring, raising the possibility of targeting macrophages to treat chronic HBV patients.

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