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Mouse Hepatitis Virus (mouse + hepatitis_virus)
Selected AbstractsExpression, crystallization and preliminary crystallographic study of mouse hepatitis virus (MHV) nucleocapsid protein C-terminal domainACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 6 2010Xiaohang Tong Mouse hepatitis virus (MHV) belongs to the group II coronaviruses. The virus produces nine genes encoding 11 proteins that could be recognized as structural proteins and nonstructural proteins and are crucial for viral RNA synthesis. The nucleocapsid (N) protein, one of the structural proteins, interacts with the 30.4,kb virus genomic RNA to form the helical nucleocapsid and associates with the membrane glycoprotein via its C-terminus to stabilize virion assembly. Here, the expression and crystallization of the MHV nucleocapsid protein C-terminal domain are reported. The crystals diffracted to 2.20,Å resolution and belonged to space group P422, with unit-cell parameters a = 66.6, c = 50.8,Å. Assuming the presence of two molecules in the asymmetric unit, the solvent content is 43.0% (VM = 2.16,Å3,Da,1). [source] Synergistic antiviral effect of a combination of mouse interferon-, and interferon-, on mouse hepatitis virusJOURNAL OF MEDICAL VIROLOGY, Issue 2 2003Uichiro Fuchizaki Abstract Although interferon (IFN)-, and IFN-, have been reported to exhibit a synergistic antiviral effect through the different signaling pathways in vitro, their therapeutic efficacy is not well defined in vivo. The current study was carried out to investigate the combined antiviral effect in a model of mouse hepatitis virus Type 2 (MHV-2) infection, in which fulminant hepatitis is developed. MHV-2 was injected intraperitoneally into 4-week-old ICR mice, IFN or the vehicle was administered intramuscularly for 5 days, and the antiviral effect was evaluated based on survival periods, liver histology, serum alanine transaminase (ALT) levels, and MHV-2 virus titers in the liver tissues. The animals in the group treated with a combination of IFN-, and IFN-, survived for longer periods than the groups treated with IFN-, alone and IFN-, alone (IFN-, 103 (IU/mouse)/-, 103 vs. IFN-, 103, P,<,0.005; IFN-, 103/-, 103 vs. IFN-, 103, P,<,0.001). This is consistent with the lower levels of hepatocellular necrosis and serum ALT and the decreased titers of MHV-2 virus in the liver tissues (48 hr, P,<,0.001; 72 hr, P,<,0.001). These findings indicate that a combination of IFN-, and IFN-, exhibits a synergistic antiviral effect on MHV-2 infection. The biology of MHV-2 is quite different from that of human hepatitis viruses; however, these results suggest the beneficial combined therapy of IFN-, and IFN-, for the treatment of human viral hepatitis. J. Med. Virol. 69:188,194, 2003. © 2003 Wiley-Liss, Inc. [source] Astrocyte expression of a dominant-negative interferon-, receptorJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2005Claudia Hindinger Abstract Interferon-, (IFN-,) is a major proinflammatory cytokine, and binding to its nearly ubiquitous receptor induces a wide variety of biological functions. To explore the role(s) of IFN-, signaling in astrocytes, transgenic mice (GFAP/IFN-,R1,IC) expressing a dominant-negative IFN-, receptor alpha chain under control of the astrocyte-specific glial fibrillary acid protein (GFAP) promoter were generated. Transgenic mice developed normally, had normal astrocyte numbers and distribution, and exhibited no clinically overt phenotype. Transgene mRNA expression was detected only in the CNS, and the transgene-encoded IFN-, receptor 1 colocalized with GFAP, which is consistent with astrocyte expression. Astrocytes from transgenic mice exhibited reduced IFN-,-induced signaling as measured by major histocompatibility class II induction. Neither CNS inflammation nor perforin-mediated clearance of a neurotropic mouse hepatitis virus from astrocytes was impaired following infection. Transgenic mice with impaired astrocyte responsiveness to IFN-, provide a model for studying the selective astrocyte-dependent effects of this critical cytokine in CNS immunopathology. © 2005 Wiley-Liss, Inc. [source] Cytopathy of an infiltrating monocyte lineage during the early phase of infection with murinecoronavirus in the brainNEUROPATHOLOGY, Issue 4 2010Hanae Takatsuki Viral spread during the early stages after infection was compared between a highly neurovirulent mouse hepatitis virus (MHV), JHMV cl-2 strain (cl-2), and its low-virulent mutant, soluble-receptor-resistant (srr)7. The infection of cells with srr7 (soluble-receptor-resistant mutant 7) is dependent on a known MHV receptor (MHVR), carcinoembryonic cell adhesion molecule 1a, whereas cl-2 shows MHVR-independent infection. Initial viral antigens were detected between 12 and 24 h post-inoculation (p.i) in the infiltrating cells that appeared in the subarachnoidal space of mouse brains infected with viruses. There were no significant differences in the intensity or spread of viral antigens in the inflammatory cells between the two viruses. However, 48 h after infection with cl-2, viral antigen-positive cells in the grey matter with the shape of neurons, which do not express MHVR, were detected, while srr7 infection was observed primarily in the white matter. Some of the viral antigen-positive inflammatory cells found in the subarachnoidal space during the early phase of infection reacted with anti-F4/80 or anti-CD11b monoclonal antibodies. Syncytial giant cells (SGCs) expressing viral and CD11b antigens were also detected among these inflammatory cells. These antigen-positive cells appeared in the subarachnoidal space prior to viral antigen spread into the brain parenchyma, indicating that viral encephalitis starts with the infection of infiltrating monocytes which express MHVR. Furthermore, the observation indicates that viral infection has cytopathic effects on the monocyte lineage, which plays a critical role in innate immunity, leading to the rapid spread of viruses during the early stage of infection. [source] Expression, crystallization and preliminary crystallographic study of mouse hepatitis virus (MHV) nucleocapsid protein C-terminal domainACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 6 2010Xiaohang Tong Mouse hepatitis virus (MHV) belongs to the group II coronaviruses. The virus produces nine genes encoding 11 proteins that could be recognized as structural proteins and nonstructural proteins and are crucial for viral RNA synthesis. The nucleocapsid (N) protein, one of the structural proteins, interacts with the 30.4,kb virus genomic RNA to form the helical nucleocapsid and associates with the membrane glycoprotein via its C-terminus to stabilize virion assembly. Here, the expression and crystallization of the MHV nucleocapsid protein C-terminal domain are reported. The crystals diffracted to 2.20,Å resolution and belonged to space group P422, with unit-cell parameters a = 66.6, c = 50.8,Å. Assuming the presence of two molecules in the asymmetric unit, the solvent content is 43.0% (VM = 2.16,Å3,Da,1). [source] Cell permeabilization by poliovirus 2B viroporin triggers bystander permeabilization in neighbouring cells through a mechanism involving gap junctionsCELLULAR MICROBIOLOGY, Issue 8 2010Vanesa Madan Summary Poliovirus 2B protein is a well-known viroporin implicated in plasma membrane permeabilization to ions and low-molecular-weight compounds during infection. Translation in mammalian cells expressing 2B protein is inhibited by hygromycin B (HB) but remains unaffected in mock cells, which are not permeable to the inhibitor. Here we describe a previously unreported bystander effect in which healthy baby hamster kidney (BHK) cells become sensitive to HB when co-cultured with a low proportion of cells expressing poliovirus 2B. Viroporins E from mouse hepatitis virus, 6K from Sindbis virus and NS4A protein from hepatitis C virus were also able to permeabilize neighbouring cells to different extents. Expression of 2B induced permeabilization of neighbouring cell lines other than BHK. We found that gap junctions are responsible mediating the observed bystander permeabilization. Gap junctional communication was confirmed in 2B-expressing co-cultures by fluorescent dye transfer. Moreover, the presence of connexin 43 was confirmed in both mock and 2B-transfected cells. Finally, inhibition of HB entry to neighbouring cells was observed with 18,-glycyrrhethinic acid, an inhibitor of gap junctions. Taken together, these findings support a mechanism involving gap junctional intercellular communication in the bystander permeabilization effect observed in healthy cells co-cultured with poliovirus 2B-expressing cells. [source] Qualitative and quantitative ultrastructural analysis of the membrane rearrangements induced by coronavirusCELLULAR MICROBIOLOGY, Issue 6 2010Mustafa Ulasli Summary Coronaviruses (CoV) are enveloped positive-strand RNA viruses that induce different membrane rearrangements in infected cells in order to efficiently replicate and assemble. The origin, the protein composition and the function of these structures are not well established. To shed further light on these structures, we have performed a time-course experiment in which the mouse hepatitis virus (MHV)-induced membrane rearrangements were examined qualitatively and quantitatively by (immuno)-electron microscopy. With our approach we were able to confirm the appearance of 6, previously reported, membranous structures during the course of a complete infection cycle. These structures include the well-characterized double-membrane vesicles (DMVs), convoluted membranes (CMs) and virions but also the more enigmatic large virion-containing vacuoles (LVCVs), tubular bodies (TBs) and cubic membrane structures (CMSs). We have characterized the LVCVs, TBs and CMSs, and found that the CoV-induced structures appear in a strict order. By combining these data with quantitative analyses on viral RNA, protein synthesis and virion release, this study generates an integrated molecular and ultrastructural overview of CoV infection. In particular, it provides insights in the role of each CoV-induced structure and reveals that LVCVs are ERGIC/Golgi compartments that expand to accommodate an increasing production of viral particles. [source] Regulation of cell death during infection by the severe acute respiratory syndrome coronavirus and other coronavirusesCELLULAR MICROBIOLOGY, Issue 11 2007Yee-Joo Tan Summary Both apoptosis and necrosis have been observed in cells infected by various coronaviruses, suggesting that the regulation of cell death is important for viral replication and/or pathogenesis. Expeditious research on the severe acute respiratory syndrome (SARS) coronavirus, one of the latest discovered coronaviruses that infect humans, has provided valuable insights into the molecular aspects of cell-death regulation during infection. Apoptosis was observed in vitro, while both apoptosis and necrosis were observed in tissues obtained from SARS patients. Viral proteins that can regulate apoptosis have been identified, and many of these also have the abilities to interfere with cellular functions. Occurrence of cell death in host cells during infection by other coronaviruses, such as the mouse hepatitis virus and transmissible porcine gastroenteritis virus, has also being extensively studied. The diverse cellular responses to infection revealed the complex manner by which coronaviruses affect cellular homeostasis and modulate cell death. As a result of the complex interplay between virus and host, infection of different cell types by the same virus does not necessarily activate the same cell-death pathway. Continuing research will lead to a better understanding of the regulation of cell death during viral infection and the identification of novel antiviral targets. [source] | ||||||||||