Receptor-Independent Spread of a Highly Neurotropic Murine Coronavirus JHMV Strain from Initially Infected Microglial Cells in Mixed Neural Cultures

Nakagaki, Keiko; Nakagaki, Kazuhide; Taguchi, Fumihiro

doi:10.1128/jvi.79.10.6102-6110.2005

Cited by 50 publications

(63 citation statements)

References 37 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Compared with the S1 protein of srr7, Mu-3 has a single amino acid substitution in the S1 protein region (aa 596, Asn to Lys), similar to other reported mutants, which have 1 or 2 substitutions of amino acids in the S protein region (7), the infectivity to neurons (Figs. 3B and 3F), which do not express the major MHV-receptor CEACAM1 (20). Furthermore, although Mu-3 as well as the other mutants proliferated in the brain and liver in almost a similar manner, they exhibited a higher virulence than the maternal srr7 virus, which shows MHVRdependent infectivity (Fig.…”

Section: Discussionmentioning

confidence: 94%

“…3G). MoCs or microglia is the initial target of infection by srr7 and cl-2 detected in primary brain cultures (20) and an in vivo study (3). The presence of infected F4/80 ＋ cells was detected in the meningeal region at 12 h post-inoculation, which was accompanied by cytopathy of F4/80 ＋ cells (3).…”

Section: Discussionmentioning

confidence: 99%

“…Antibodies: Viral antigens were visualized using the rabbit polyclonal antibody SP-4 or mouse monoclonal antibody (MAb) (1,20). For identification of apoptotic cell types, mouse anti-neuronal nuclei (NeuN) biotinconjugated monoclonal antibody (CHEMICON International Inc., Temecula, Calif., USA), rat antimouse biotin-conjugated CD11b (BD Pharmingen, San Diego, Calif., USA), and rabbit anti-caspase 3 (Cas3) (Millipore, Temecula, Calif., USA) were used.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Mutant Murine Hepatitis Virus-Induced Apoptosis in the Hippocampus

2014

View full text Add to dashboard Cite

SUMMARY:The mutant virus Mu-3 was isolated from the soluble receptor-resistant mutant 7 virus (srr7), which is a neuropathogenic strain of the mouse hepatitis virus JHMV, and cloned as a soluble receptor-resistant mutant from the highly neuropathogenic JHMV strain cl-2 virus (cl-2). In order to identify specific characteristcs of Mu-3, the pathology of Mu-3-infected mice was compared with that of srr7-and cl-2-infected mice. The neuropathology after Mu-3 infection exhibited a mixed pattern comparable to that induced by srr7 and cl-2 infections. In addition, Mu-3 infection caused marked apoptotic lesions in the hippocampal region, particularly in the CA2 and CA3 subregions, in the brains of all infected mice. In contrast, in cl-2 infection, 10-20z of the infected mice exhibited apoptosis in the hippocampus, which was primarily observed in the CA1 subregion. Apoptosis also occurred in the pyramidal neurons and CD11b-bearing cells. The apoptotic cells, indicated by caspase 3-activation, were a mixed population of infected and a higher number of uninfected cells. These data indicated that apoptosis observed in Mu-3 infection could be induced by the indirect effects of infection in addition to direct effects of the infected cells occurring in a cell-autonomous manner.

show abstract

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Mutant Murine Hepatitis Virus-Induced Apoptosis in the Hippocampus

2014

View full text Add to dashboard Cite

show abstract

“…It should be noted that most of the syncytia formed after infection of TGPECs expressed Gr-1 antigen. The main target among leukocytes of MHV-JHM infection has been believed to be the lineages of Mo/Mas, including microglia in the brain (5,29), which express CEACAM1. CEACAM1 is also detectable as an adhesion molecule on Gr-1-positive human granulocytes (22).…”

Section: Discussionmentioning

confidence: 99%

Contribution of Lewis X Carbohydrate Structure to Neuropathogenic Murine Coronaviral Spread

et al. 2016

View full text Add to dashboard Cite

“…For example, a pregnancy-specific glycoprotein expressed within the brain can support MHV binding and internalization (14). In addition, cellular tropism may be extended to non-CEACAM-1 bearing cells through cell-to-cell contact mediated by fusion of the S protein with adjacent cells (15)(16)(17). The biological relevance of alternative mechanisms of viral entry is also supported by low level expression of CEACAM-1 within the mouse CNS relative to other tissues, such as epithelial and endothelial cells lining the respiratory and digestive tracts (18), and the fact that expression has only been demonstrated on the endothelial cells of the cerebral blood vessels (19) and microglia (20).…”

Section: Introductionmentioning

confidence: 99%

Mouse hepatitis virus infection of the CNS: a model for defense, disease, and repair

2008

View full text Add to dashboard Cite

Viral infection of the central nervous system (CNS) results in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences. One of the principal factors that directs the outcome of infection is the localized innate immune response, which is proceeded by the adaptive immune response against the invading viral pathogen. The role of the immune system is to contain and control the spread of virus within the CNS, and paradoxically, this response may also be pathological. Studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV) have provided important insights into how the immune system combats neuroinvasive viruses, and have identified molecular and cellular mechanisms contributing to chronic disease in persistently infected mice. KeywordsVirus; Central Nervous System; Host-Defense; Disease; Chemokines; Cytokines; Review INTRODUCTIONMHV is a member of the Coronaviridae family, which represents a ubiquitous group of positive-strand RNA viral pathogens of humans and animals associated with a widespectrum of respiratory, gastrointestinal, and neurological diseases (1-4). All coronaviruses are enveloped with the largest known RNA genome identified (27-31 kb). Human coronavirus (HCoV) infections cause acute enteritis and a significant percentage (up to 34%) of all common colds; and it is important to note that a new strain of HCoV also had dramatic impact on human disease as the etiological agent of severe acute respiratory syndrome (SARS) (4-6). In addition, previously unclassified human coronaviruses associated with respiratory disease have been identified (7-9). As a natural pathogen of mice, MHV primarily infects the liver and CNS resulting in a range of acute and chronic diseases, including hepatitis, encephalitis and encephalomyelitis associated with demyelination (1-3).Send correspondence to: Dr. Thomas E. Lane, Department of Molecular Biology and Biochemistry, 3205 McGaugh Hall, University of California, Irvine, Irvine, CA 92697-3900, Tel: 949-824-5878, Fax: 949-825-8551, tlane@uci.edu. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptViral tropism and disease depends on a variety of factors, such as the strain of the virus, genetic background and age of mouse, as well as the route of infection (3).The genome and structure of MHV is characteristic of other coronaviruses with similar organization of open reading frames (ORFs) encoding structural and non-structural proteins ( Figure 1). Viral replication occurs exclusively in the cytoplasm of infected cells and is mediated at the genomic level by a virally encoded RNA-dependent RNA polymerase translated from ORF1 of the MHV genome. The three predominant MHV structural proteins are the nucleocapsid protein (N; 60 kDa), which complexes with the genome in a helical manner, the membrane protein (M; 25 kDa) that is important for envelope formation and viral budding, and the spike or surface protein (S; 180 kDa) necessary for receptor binding, cell fusion, and determinat...

show abstract

Receptor-Independent Spread of a Highly Neurotropic Murine Coronavirus JHMV Strain from Initially Infected Microglial Cells in Mixed Neural Cultures

Cited by 50 publications

References 37 publications

Mutant Murine Hepatitis Virus-Induced Apoptosis in the Hippocampus

Mutant Murine Hepatitis Virus-Induced Apoptosis in the Hippocampus

Contribution of Lewis X Carbohydrate Structure to Neuropathogenic Murine Coronaviral Spread

Mouse hepatitis virus infection of the CNS: a model for defense, disease, and repair

Contact Info

Product

Resources

About