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Li W.,China National Institute of Biological Sciences
Annual Review of Cell and Developmental Biology | Year: 2015

Hepatitis B virus (HBV) infection affects 240 million people worldwide. A liver-specific bile acid transporter named the sodium taurocholate cotransporting polypeptide (NTCP) has been identified as the cellular receptor for HBV and its satellite, the hepatitis D virus (HDV). NTCP likely acts as a major determinant for the liver tropism and species specificity of HBV and HDV at the entry level. NTCP-mediated HBV entry interferes with bile acid transport in cell cultures and has been linked with alterations in bile acid and cholesterol metabolism in vivo. The human liver carcinoma cell line HepG2, complemented with NTCP, now provides a valuable platform for studying the basic biology of the viruses and developing treatments for HBV infection. This review summarizes critical findings regarding NTCP's role as a viral receptor for HBV and HDV and discusses important questions that remain unanswered. © 2015 by Annual Reviews. All rights reserved. Source

Sun L.,CAS Shanghai Institutes for Biological Sciences | Wang X.,China National Institute of Biological Sciences
Trends in Biochemical Sciences | Year: 2014

Classically, there are two major forms of cell death: necrosis, an unregulated digestion of cellular components; and apoptosis, a programmed mechanism that is promoted by caspases. However, another form of cell death has recently been identified that is inhibited by caspases, and yet occurs through a regulated mechanism, termed programmed necrosis or necroptosis. The biochemical basis of this program has begun to emerge, with the discovery of the receptor-interacting kinase RIP3 and its substrate, the pseudokinase mixed lineage kinase domain-like protein (MLKL), as core components. Furthermore, animal models have revealed significant functions for RIP3/MLKL-mediated necrotic cell death in immune responses against microbial infection and in the etiology of diseases involving tissue damage. This review discusses recent advances in our understanding of the mechanistic details and physiological functions of programmed necrosis. © 2014 Elsevier Ltd. Source

Zhao Y.,China National Institute of Biological Sciences | Shao F.,China National Institute of Biological Sciences
Immunological Reviews | Year: 2015

Bacterial flagella and type III secretion system (T3SS) are evolutionarily related molecular transport machineries. Flagella mediate bacterial motility; the T3SS delivers virulence effectors to block host defenses. The inflammasome is a cytosolic multi-protein complex that activates caspase-1. Active caspase-1 triggers interleukin-1β (IL-1β)/IL-18 maturation and macrophage pyroptotic death to mount an inflammatory response. Central to the inflammasome is a pattern recognition receptor that activates caspase-1 either directly or through an adapter protein. Studies in the past 10 years have established a NAIP-NLRC4 inflammasome, in which NAIPs are cytosolic receptors for bacterial flagellin and T3SS rod/needle proteins, while NLRC4 acts as an adapter for caspase-1 activation. Given the wide presence of flagella and the T3SS in bacteria, the NAIP-NLRC4 inflammasome plays a critical role in anti-bacteria defenses. Here, we review the discovery of the NAIP-NLRC4 inflammasome and further discuss recent advances related to its biochemical mechanism and biological function as well as its connection to human autoinflammatory disease. © 2015 John Wiley & Sons A/S. Source

Zhao Y.,China National Institute of Biological Sciences | Shao F.,China National Institute of Biological Sciences
Current Opinion in Microbiology | Year: 2016

The inflammasomes are emerging cytosolic defenses against bacterial infections. The inflammasomes converge on inflammatory caspases activation that triggers pyroptosis, and interleukin-1β/18 maturation in the case of caspase-1 activation. The inflammasomes not only detect major bacterial molecules but also sense bacterial virulence activity. Among the canonical caspase-1-activating inflammasomes, the NAIP subfamily of NLR proteins serves as the receptors for bacterial flagellin and type III secretion apparatus; Pyrin indirectly senses Rho modification/inactivation by various bacterial agents; NLRP1 in mice/rats detects the protease activity of anthrax lethal toxin by serving as its substrate. Caspase-11 and caspase-4/5 directly recognize bacterial LPS and then become activated. Inflammasome sensing of cytosolic bacteria employs much more diversified biochemical mechanisms, compared with Toll-like receptors-mediated recognition on the membrane. © 2015 Elsevier Ltd. Source

Zhang J.,China National Institute of Biological Sciences | Zhou J.-M.,China National Institute of Biological Sciences
Molecular Plant | Year: 2010

Pathogen/microbe-associated molecular patterns (PAMPs/MAMPs) are recognized by host cell surface-localized pattern-recognition receptors (PRRs) to activate plant immunity. PAMP-triggered immunity (PTI) constitutes the first layer of plant immunity that restricts pathogen proliferation. PTI signaling components often are targeted by various Pseudomonas syringae virulence effector proteins, resulting in diminished plant defenses and increased bacterial virulence. Some of the proteins targeted by pathogen effectors have evolved to sense the effector activity by associating with cytoplasmic immune receptors classically known as resistance proteins. This allows plants to activate a second layer of immunity termed effector-triggered immunity (ETI). Recent studies on PTI regulation and P. syringae effector targets have uncovered new components in PTI signaling. Although MAP kinase (MAPK) cascades have been considered crucial for PTI, emerging evidence indicates that a MAPK-independent pathway also plays an important role in PTI signaling. © 2010 The Author. Source

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