Differential effects of rabies and borna disease viruses on immediate-early- and late-response gene expression in brain tissues

Fu, Zhen F.; Weihe, Eberhard; Zheng, Yun‐Min; Schäfer, Martin; Sheng, Hai; Corisdeo, Susanne; Rauscher, Frank J.; Koprowski, Hilary; Dietzschold, Bernhard

doi:10.1128/jvi.67.11.6674-6681.1993

Cited by 79 publications

(22 citation statements)

References 38 publications

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“…6B). It has also been reported that there is a good correlation between Egr-1 and viral RNA expressions in the mouse brains infected with Rabies and Borna disease viruses, which raises the possibility that Egr-1 expression may induce some phenotypic changes in neurons that render them more susceptible to viral replication (Fu et al, 1993). The other potential consequence of Egr-1 induction is to promote host cell proliferation and survival.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, in addition to MHV as found in this study, it has been shown that Egr-1 gene expression is induced by infections with diverse groups of viruses. For example, Egr-1 expression was induced in the brain tissue in experimental mice infected with Rabies virus and Borna disease virus (BDV), in a number of human cells infected with human foamy virus (HFV), in human T-cell leukemia virus type 1-(HTLV-1) or type 2 (HTLV-2)transformed cell lines, in B-lymphocytes infected with Epstein-Barr virus (EBV), and in Bc-2 cells latently infected with Kaposi's sarcoma-associated herpesvirus (KSHV) (Fu et al, 1993;Wagner et al, 2000;Calogero et al, 1996;Wright et al, 1990;Sukhatme et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

2006

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“…Egr-1 is involved in the gene expression and the replication of several viruses such as Epstein Barr virus [31,32], HSV-1 [17,33,34], JC virus [35], orthopox virus [36], murine corona virus [37], rabies virus [38,39], borna disease virus [39], human foamy virus [40], Japanese encephalitis virus [38], HTLV-I [41,42] and HTLV-II [42]. In most cases, Egr-1 was induced after the virus targeted neural cells and lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Lytic HSV-1 infection induces the multifunctional transcription factor Early Growth Response-1 (EGR-1) in rabbit corneal cells

Bedadala

Palem

Graham

et al. 2011

Virol J

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BackgroundHerpes simplex virus type-1 (HSV-1) infections can cause a number of diseases ranging from simple cold sores to dangerous keratitis and lethal encephalitis. The interaction between virus and host cells, critical for viral replication, is being extensively investigated by many laboratories. In this study, we tested the hypothesis that HSV-1 lytic infection triggers the expression of important multi-functional transcription factor Egr1. The mechanisms of induction are mediated, at least in part, by signaling pathways such as NFκB and CREB.MethodsSIRC, VERO, and 293HEK cell lines were infected with HSV-1, and the Egr-1 transcript and protein were detected by RT-PCR and Western blot, respectively. The localization and expression profile of Egr-1 were investigated further by immunofluorescence microscopy analyses. The recruitment of transcription factors to the Egr-1 promoter during infection was studied by chromatin immunoprecipitation (ChIP). Various inhibitors and dominant-negative mutant were used to assess the mechanisms of Egr-1 induction and their effects were addressed by immunofluorescence microscopy.ResultsWestern blot analyses showed that Egr-1 was absent in uninfected cells; however, the protein was detected 24-72 hours post treatment, and the response was directly proportional to the titer of the virus used for infection. Using recombinant HSV-1 expressing EGFP, Egr-1 was detected only in the infected cells. ChIP assays demonstrated that NFкB and cAMP response element binding protein (CREB) were recruited to the Egr-1 promoter upon infection. Additional studies showed that inhibitors of NFкB and dominant-negative CREB repressed the Egr-1 induction by HSV-1 infection.ConclusionCollectively, these results demonstrate that Egr-1 is expressed rapidly upon HSV-1 infection and that this novel induction could be due to the NFкB/CREB-mediated transactivation. Egr-1 induction might play a key role in the viral gene expression, replication, inflammation, and the disease progression.

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“…In contrast, HEP-RANTES and particularly HEP-IP10 not only induced high and persistent expression of the intended chemokines but also induced high expression of other chemokines. High and persistent infiltration of inflammatory cells, particularly neutrophils and T cells, was also observed in the CNS, which can produce neurotoxins, free radicals, and proinflammatory cytokines, causing CNS destruction (13).…”

Section: Discussionmentioning

confidence: 99%

The Roles of Chemokines in Rabies Virus Infection: Overexpression May Not Always Be Beneficial

Zhao

Toriumi²,

Kuang³

et al. 2009

J Virol

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It was found previously that induction of innate immunity, particularly chemokines, is an important mechanism of rabies virus (RABV) attenuation. To evaluate the effect of overexpression of chemokines on RABV infection, chemokines macrophage inflammatory protein 1␣ (MIP-1␣), RANTES, and IP-10 were individually cloned into the genome of attenuated RABV strain HEP-Flury. These recombinant RABVs were characterized in vitro for growth properties and expression of chemokines. It was found that all the recombinant viruses grew as well as the parent virus, and each of the viruses expressed the intended chemokine in a dose-dependent manner. When these viruses were evaluated for pathogenicity in the mouse model, it was found that overexpression of MIP-1␣ further decreased RABV pathogenicity by inducing a transient innate immune response. In contrast, overexpression of RANTES or IP-10 increased RABV pathogenicity by causing neurological diseases, which is due to persistent and high-level expression of chemokines, excessive infiltration and accumulation of inflammatory cells in the central nervous system, and severe enhancement of blood-brain barrier permeability. These studies indicate that overexpression of chemokines, although important in controlling virus infection, may not always be beneficial to the host.Rabies virus (RABV) is a negative-strand RNA virus belonging to the Rhabidoviridae family, genus Lyssavirus, which causes rabies (fatal encephalomyelitis) in many species of mammals (5). More than 55,000 humans die of rabies each year worldwide (26). Once clinical signs develop, rabies is always fatal (12, 53). Despite the lethality of rabies, only mild inflammation and little neuronal destruction were observed in the central nervous system (CNS) of rabies patients (31, 32). Adaptation of wild-type (wt) RABV in laboratory animals and/or cell culture leads to attenuation in phenotype, and laboratory-adapted RABVs have been used for vaccine development (1, 10). To delineate the mechanism(s) of RABV attenuation, previous studies compared the host responses to infection with either laboratory-attenuated or wt RABV (52). It was found that laboratory-attenuated RABV induced extensive inflammation, apoptosis, and neuronal degeneration, as well as induction of expression of innate immune genes in the CNS; however, wt RABV caused little or no neuronal damage and avoided the activation of expression of innate molecule genes. Other investigators also reported the induction of innate immunity in mice or neuronal cells infected with laboratory-attenuated viruses (20,33,37). The mostly upregulated genes in the innate immune responses after infection with attenuated RABV include genes encoding for inflammatory chemokines and type I interferon (IFN) as well as 33, 378). Further studies have shown that the expression of chemokines (mRNA and proteins), particularly macrophage inflammatory protein 1␣ (MIP-

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Differential effects of rabies and borna disease viruses on immediate-early- and late-response gene expression in brain tissues

Cited by 79 publications

References 38 publications

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

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

Lytic HSV-1 infection induces the multifunctional transcription factor Early Growth Response-1 (EGR-1) in rabbit corneal cells

The Roles of Chemokines in Rabies Virus Infection: Overexpression May Not Always Be Beneficial

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