Regulation of Matrix Metalloproteinase (MMP) and Tissue Inhibitor of Matrix Metalloproteinase (TIMP) Genes During JHMV Infection of the Central Nervous System

Zhou, Jiehao; Stohlman, Stephen A.; Marten, Norman W.; Hinton, David R.

doi:10.1007/978-1-4615-1325-4_49

Cited by 4 publications

(3 citation statements)

References 12 publications

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“…Oligodendroglia were gated out from the CD45 Ϫ population using anti-O4 monoclonal Ab. The percentage of astrocytes in the enriched population is ϳ60% (76). A minimum of 10 5 cells collected per population were frozen in 400 l of Trizol (Invitrogen, Carlsbad, CA) at Ϫ80°C for subsequent RNA extraction and PCR analysis as described previously (23).…”

Section: Mice and Infectionmentioning

confidence: 99%

Factors Supporting Intrathecal Humoral Responses following Viral Encephalomyelitis

Phares

Marques

Stohlman

et al. 2011

J Virol

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Central nervous system (CNS) infections and autoimmune inflammatory disorders are often associated with retention of antibody-secreting cells (ASC). Although beneficial or detrimental contributions of ASC to CNS diseases remain to be defined, virus-specific ASC are crucial in controlling persistent CNS infection following coronavirus-induced encephalomyelitis. This report characterizes expression kinetics of factors associated with ASC homing, differentiation, and survival in the spinal cord, the prominent site of coronavirus persistence. Infection induced a vast, gamma interferon (IFN-␥)-dependent, prolonged increase in chemokine (C-X-C motif) ligand 9 (CXCL9), CXCL10, and CXCL11 mRNA, supporting a role for chemokine (C-X-C motif) receptor 3 (CXCR3)-mediated ASC recruitment. Similarly, CD4 T cell-secreted interleukin-21, a critical regulator of both peripheral activated B cells and CD8 T cells, was sustained during viral persistence. The ASC survival factors B cell-activating factor of the tumor necrosis factor (TNF) family (BAFF) and a proliferatinginducing ligand (APRIL) were also significantly elevated in the infected CNS, albeit delayed relative to the chemokines. Unlike IFN-␥-dependent BAFF upregulation, APRIL induction was IFN-␥ independent. Moreover, both APRIL and BAFF were predominantly localized to astrocytes. Last, the expression kinetics of the APRIL and BAFF receptors coincided with CNS accumulation of ASC. Therefore, the factors associated with ASC migration, differentiation, and survival are all induced during acute viral encephalomyelitis, prior to ASC accumulation in the CNS. Importantly, the CNS expression kinetics implicate rapid establishment, and subsequent maintenance, of an environment capable of supporting differentiation and survival of protective antiviral ASC, recruited as plasmablasts from lymphoid organs.Virus-specific antibodies (Ab) play an important role in the control of many viral infections of the central nervous system (CNS) (17). Ab are delivered to the CNS either by diffusion across a compromised blood brain barrier (18, 53) or actively by Ab-secreting cells (ASC) which have infiltrated the CNS or differentiated locally in the inflamed tissue. Passage of Ab from serum is inefficient under steady-state conditions, making ASC-mediated Ab secretion at the site of CNS infection a more effective strategy of viral control. For example, Ab production by invading B cells is required to clear rabies virus from the CNS, as passively administered Ab do not mediate virus clearance (22). Furthermore, B cells in the CNS of Sindbis virus-infected mice continue to secrete Ab during viral RNA persistence, supporting the idea that ASC play a role in preventing viral recrudescence (71). In addition, prolonged intrathecal antiviral Ab production and ASC accumulation within the CNS occur following control of Semliki Forest virus (43, 53-55), measles virus (9, 48), and Theiler's murine encephalomyelitis virus (50, 51) infections.The concept of an ASC survival niche in the CNS during chronic infl...

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Section: Mice and Infectionmentioning

confidence: 99%

Factors Supporting Intrathecal Humoral Responses following Viral Encephalomyelitis

Phares

Marques

Stohlman

et al. 2011

J Virol

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“…Astrocytes can be stimulated to produce diverse proinflammatory molecules such as cytokines, chemokines, and nitric oxide (Van Wagoner and Benveniste, 1999;Huang et al, 2000;Chen and Swanson, 2003). It has been shown that MHV infection can induce the expression of transforming necrosis factor (TNF)-α, interleukin (IL)-6, matrix metalloproteinases, and inducible nitric oxide synthase (iNOS) in astrocytes (Kyuwa et al, 1994;Joseph et al, 1993;Zhou et al, 2001;Grzybicki et al, 1997). Infection of astrocytes with MHV may thus modulate the development of the CNS pathology and alter the course of the disease.…”

Section: Introductionmentioning

confidence: 99%

Induction of transcription factor Egr-1 gene expression in astrocytoma cells by Murine coronavirus infection

2006

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Mouse hepatitis virus (MHV) causes encephalitis and demyelination in the central nervous system (CNS) of susceptible rodents. Astrocytes are one of the major targets for MHV infection in the CNS, and respond to MHV infection by expressing diverse molecules that may contribute to CNS pathogenesis. Here we characterized the activation of an immediate-early transcription factor Egr-1 by MHV infection in an astrocytoma cell line. We found that the expression of Egr-1 was dramatically increased following virus infection. Using various inhibitors of mitogen-activated protein kinases, we identified that the extracellular signal-regulated kinases 1/2 were involved in the activation of Egr-1 transcription by MHV infection. Experiments with ultraviolet light-inactivated virus revealed that the induction of Egr-1 did not require virus replication and was likely mediated during cell entry. We further found that over-expression of Egr-1 suppressed the expression of BNip3, a pro-apoptotic member of the Bcl-2 family. This finding may provide an explanation for our previously observed down-regulation of BNip3 by MHV infection in astrocytoma cells (Cai, Liu, Yu, and Zhang, Virology 316:104-115, 2003). Furthermore, knockdown of Egr-1 by an siRNA inhibited MHV propagation, suggesting the biological relevance of Egr-1 induction to virus replication. In addition, the persistence/demylinating-positive strains (JHM and A59) induced Egr-1 expression, whereas the persistence/demylinating-negative strain (MHV-2) did not. These results indicate a correlation between the ability of MHVs to induce Egr-1 expression and their ability to cause demyelination in the CNS, which may suggest a potential role for the induction of Egr-1 in viral pathogenesis.

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“…Because astrocyte is one of the antigen-presenting cells in the CNS (Fierz et al, 1985), it can produce diverse proinflammatory molecules such as cytokines, chemokines, and nitric oxide upon stimulation (Van Wagoner and Benveniste, 1999;Huang et al, 2000;Chen and Swanson, 2003). It has been shown that coronaviruses induce the expression of transforming necrosis factor-(TNF) ␣, interleukin-(IL) 6, matrix metalloproteinases, and inducible nitric oxide synthase in primary and established astrocytes (Joseph et al, 1993;Zhou et al, 2001;Grzybicki et al, 1997;Kyuwa et al, 1994). Thus, it is conceivable that infection of astrocytes with MHV can modulate the development of the CNS pathology and alter the course of the disease.…”

Section: Introductionmentioning

confidence: 99%

Down-regulation of transcription of the proapoptotic gene BNip3 in cultured astrocytes by murine coronavirus infection

Caì

Yin

et al. 2003

Virology

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Murine coronavirus mouse hepatitis virus (MHV) causes encephalitis and demyelination in the central nervous system of susceptible rodents. Astrocytes are the major target for MHV persistence. However, the mechanisms by which astrocytes survive MHV infection and permit viral persistence are not known. Here we performed DNA microarray analysis on differential gene expression in astrocyte DBT cells by MHV infection and found that the mRNA of the proapoptotic gene BNip3 was significantly decreased following MHV infection. This finding was further confirmed by quantitative reverse transcription-polymerase chain reaction, Western blot analysis, and BNip3-promoter-luciferase reporter system. Interestingly, infection with live and ultraviolet light-inactivated viruses equally repressed BNip3 expression, indicating that the down-regulation of BNip3 expression does not require virus replication and is mediated during cell entry. Furthermore, treatment of cells with chloroquine, which blocks the acidification of endosomes, significantly inhibited the repression of the BNip3 promoter activity induced by the acidic pH-dependent MHV mutant OBLV60, which enters cells via endocytosis, indicating that the down-regulation of BNip3 expression is mediated by fusion between viral envelope and cell membranes during entry. Deletion analysis showed that the sequence between nucleotides 262 and 550 of the 588-base-pair BNip3 promoter is necessary and sufficient for driving the BNip3 expression and that it contains signals that are responsible for MHV-induced down-regulation of BNip3 expression in DBT cells. These results may provide insights into the mechanisms by which MHV evades host antiviral defense and promotes cell survival, thereby allowing its persistence in the host astrocytes.

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Regulation of Matrix Metalloproteinase (MMP) and Tissue Inhibitor of Matrix Metalloproteinase (TIMP) Genes During JHMV Infection of the Central Nervous System

Cited by 4 publications

References 12 publications

Factors Supporting Intrathecal Humoral Responses following Viral Encephalomyelitis

Factors Supporting Intrathecal Humoral Responses following Viral Encephalomyelitis

Induction of transcription factor Egr-1 gene expression in astrocytoma cells by Murine coronavirus infection

Down-regulation of transcription of the proapoptotic gene BNip3 in cultured astrocytes by murine coronavirus infection

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