Role of virus receptor-bearing endothelial cells of the blood-brain barrier in preventing the spread of mouse hepatitis virus-A59 into the central nervous system

Godfraind, Catherine; Havaux, N; Holmes, Kathryn V.; Coutelier, Jean Paul

doi:10.3109/13550289709031188

Cited by 28 publications

(37 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5m) might be mediated by a conduit system reaching to the splenic white pulp, 26 including to T‐cell zones 27 . Although endothelial cells express the MHV receptor and MHV can bind to endothelial cells via this receptor, 28 further careful examination is required to determine whether it is the infected endothelial cells that guide the extension of the infection into the parenchyma, perivascular fibrous apparatus comprising a conduit system, or if monocyte lineages play an important role. Infiltrated monocytes which stick to the blood vessels are often indistinguishable from endothelial cells on light microscopic observation 29 …”

Section: Discussionmentioning

confidence: 99%

Cytopathy of an infiltrating monocyte lineage during the early phase of infection with murinecoronavirus in the brain

et al. 2009

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Cytopathy of an infiltrating monocyte lineage during the early phase of infection with murinecoronavirus in the brain

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Vessel endothelial cells and perivascular cells are likely important in antigen presentation to lymphocytes being recruited into the CNS. In addition, endothelial cells express the receptor for MHV, 37,38 so they may play a role in virus dissemination throughout the CNS.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Expression of Major Histocompatibility Complex Molecules on Oligodendrocytes and Neurons during Viral Infection

Redwine

Buchmeier

Evans

2001

The American Journal of Pathology

106

View full text Add to dashboard Cite

Demyelination in multiple sclerosis and in animal models is associated with infiltrating CD8؉ and CD4؉ T cells. Although oligodendrocytes and axons are damaged in these diseases, the roles T cells play in the demyelination process are not completely understood. Antigen-specific CD8؉ T cell lysis of target cells is dependent on interactions between the T cell receptor and major histocompatibility complex (MHC) class I-peptide complexes on the target cell. In the normal central nervous system, expression of MHC molecules is very low but often increases during inflammation. We set out to precisely define which central nervous system cells express MHC molecules in vivo during infection with a strain of murine hepatitis virus that causes a chronic, inflammatory demyelinating disease. Using double immunofluorescence labeling, we show that during acute infection with murine hepatitis virus, MHC class I is expressed in vivo by oligodendrocytes, neurons, microglia, and endothelia, and MHC class II is expressed only by microglia. These data indicate that oligodendrocytes and neurons have the potential to present antigen to T cells and thus be damaged by direct antigen-specific interactions with CD8؉ T lymphocytes. Cell death associated with a local inflammatory response within the central nervous system (CNS) occurs in many neurological diseases, including multiple sclerosis (MS) and progressive multifocal leukoencephalopathy (PML) caused by JC virus.

show abstract

“…Mouse hepatitis viruses (MHV) are known to be lymphotropic, and depending on the viral strain and also on the mouse genetic background, they induce diverse alterations of the immunological system (3,8). The MHV strain A59 (MHV-A59) is a coronavirus that triggers various pathologies in susceptible mice, including hepatitis and thymus involution, IgG2a-restricted hypergammaglobulinemia, and transient demyelination (3,8).…”

Section: Introductionmentioning

confidence: 99%

“…The MHV strain A59 (MHV-A59) is a coronavirus that triggers various pathologies in susceptible mice, including hepatitis and thymus involution, IgG2a-restricted hypergammaglobulinemia, and transient demyelination (3,8).…”

Section: Introductionmentioning

confidence: 99%

Fine Specificity of Autoantibodies Induced By Mouse Hepatitis Virus A59

2009

View full text Add to dashboard Cite

We have shown that mice infected with mouse hepatitis virus A59 (MHV-A59) develop autoantibodies (autoAb) to liver and kidney fumarylacetoacetate hydrolase (FAH). The autoAb recognized conformational as well as linear antigenic determinants in the enzyme, and the autoimmune response was not entirely restricted to molecular mimicry and/or epitope spreading. Since the N- and C-terminal portions of the enzyme were the most reactive with autoAb, the fine specificity of these Ab was investigated. Immobilized 15-mer linear peptides (overlapping by 14 amino acids) spanning the N-terminal FAH sequence 1-49 were recognized by Ab from MHV-infected mice. The pattern of reactivity indicated the existence of two major epitope cores (i.e., sequences 9-23 and 30-44), and sequence comparison permitted the identification of two minimal epitopes, DSDFPIQ (amino acids 9-15) and IGDQILD (amino acids 36-42). Mutational analysis of sequences 9-23 and 30-44 indicated that residues 9-12 (DSDF) from the first major N-terminal epitope, and residue 36 (I) from the second, were the key amino acids energetically important for Ab contact. Interestingly, those residues were inside the two minimal epitopes previously predicted. The C-terminal portion of the enzyme (sequence 390-419) presented only one major epitope, located between residues 390 and 409. In this case, the minimal epitope had nine amino acids, CQGDGYRVG, corresponding to the FAH sequence 396-404 that outlines a loop specific for the enzyme. Data indicated that neither the FAH minimal epitopes nor the key residues important for binding to Ab from MHV-infected mice have their counterparts in the viral proteins. However, location of the energetically important residues in the tertiary structure of the enzyme originates a virtual conformational epitope. Such hypothetical B-cell epitopes could be present in any viral protein, originating a cross-reaction leading to the autoimmune response induced by MHV.

show abstract

Role of virus receptor-bearing endothelial cells of the blood-brain barrier in preventing the spread of mouse hepatitis virus-A59 into the central nervous system

Cited by 28 publications

References 31 publications

Cytopathy of an infiltrating monocyte lineage during the early phase of infection with murinecoronavirus in the brain

Cytopathy of an infiltrating monocyte lineage during the early phase of infection with murinecoronavirus in the brain

In Vivo Expression of Major Histocompatibility Complex Molecules on Oligodendrocytes and Neurons during Viral Infection

Fine Specificity of Autoantibodies Induced By Mouse Hepatitis Virus A59

Contact Info

Product

Resources

About