Protective effect of recombinant murine interferon beta against mouse hepatitis virus infection

Minagawa, Hiroko; Takenaka, Akira; Mohri, Satoshi; Mori, Ryoichi

doi:10.1016/0166-3542(87)90079-9

Cited by 25 publications

(22 citation statements)

References 17 publications

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“…In addition, it is also possible that the reduction in IFN-␤ transcript levels in the CNS of anti-Mig-treated mice is a reflection of reduced cellular infiltration as has been suggested by Mahalingam et al (23) in studies with a recombinant vaccinia virus expressing Mig. The increased viral burden within the CNS of mice treated with antiMig antisera is most likely the result of decreased levels of IFN-␥ and IFN-␤ as both cytokines are considered to contribute to host defense against MHV infection (5,6,42).…”

Section: Discussionmentioning

confidence: 99%

Expression of Mig (Monokine Induced by Interferon-γ) Is Important in T Lymphocyte Recruitment and Host Defense Following Viral Infection of the Central Nervous System

Liu

Armstrong²,

Hamilton³

et al. 2001

The Journal of Immunology

136

140

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Induction of a Th1 immune response against viral infection of the CNS is important in contributing to viral clearance. The present studies demonstrate a role for the T cell chemoattractant chemokine Mig (monokine induced by IFN-γ) in contributing to a Th1 response against mouse hepatitis virus infection of the CNS. Analysis of the kinetics of Mig expression revealed mRNA transcripts present at days 7 and 12 postinfection (p.i.) but not early (day 2) or late (day 35) in the infection. To determine functional significance, mouse hepatitis virus-infected mice were treated with anti-Mig antisera, and the severity of disease was evaluated. Such treatment resulted in a marked increase in mortality that correlated with a >3 log increase in viral burden within the brains as compared with control mice treated with normal rabbit serum. Anti-Mig-treated mice displayed a significant decrease (p < 0.005) in CD4+ and CD8+ T cell recruitment into the CNS as compared with normal rabbit serum-treated mice. In addition, anti-Mig treatment resulted in a significant decrease (p < 0.05) in levels of IFN-γ and IFN-β that coincided with increased (p < 0.02) expression of the anti-inflammatory Th2 cytokine IL-10 within the CNS. Collectively, these data indicate that Mig is important in contributing to host defense by promoting a protective Th1 response against viral infection of the CNS.

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Section: Discussionmentioning

confidence: 99%

Expression of Mig (Monokine Induced by Interferon-γ) Is Important in T Lymphocyte Recruitment and Host Defense Following Viral Infection of the Central Nervous System

Liu

Armstrong²,

Hamilton³

et al. 2001

The Journal of Immunology

136

140

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“…For this purpose, we examined the effects of HD-IFN on the infection of susceptible mouse strain C57/B6 with mouse coronavirus MHV-3. Treatment with recombinant mIFN-␤ type I was shown to prolong survival following MHV-2 exposure, particularly when the treatment was initiated prior to viral infection (19,22).…”

Section: Construction Of Ad Vectorsmentioning

confidence: 99%

Liver-Specific Alpha 2 Interferon Gene Expression Results in Protection from Induced Hepatitis

Aurisicchio

Delmastro

Salucci

et al. 2000

J Virol

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The current therapy for hepatitis B and C is based on systemic administration of recombinant human alpha interferon (r-hIFN-␣). However, systemic delivery of r-hIFN-␣ is associated with severe side effects, but more importantly, it is effective in only a small percentage of patients. In an effort to maximize IFN-␣ antiviral efficacy, we have explored the therapeutic potential of murine IFN-␣2 (mIFN␣2) selectively expressed in the liver. To this end, we have developed a helper-dependent adenovirus vector (HD) containing the mIFN-␣2 gene under the control of the liver-specific transthyretin promoter (HD-IFN). Comparison with a first-generation adenovirus carrying the same mIFN-␣2 expression cassette indicates that at certain HD-IFN doses, induction of antiviral genes can be achieved in the absence of detectable circulating mIFN-␣2. Challenge of injected mice with mouse hepatitis virus type 3 showed that HD-IFN provides high liver protection. Moreover, liver protection was also observed in acute nonviral liver inflammation hepatitis induced by concanavalin A at 1 month postinfection. These results hold promise for the development of a gene therapy treatment for chronic viral hepatitis based on liver-restricted expression of IFN-␣2.Interferon (IFN) was discovered by Isaac and Lindenmann in 1957 (18), and recently the U.S. Food and Drug Administration has approved recombinant human IFN-␣ (r-hIFN-␣) for the treatment of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. IFN-␣ acts on target cells to confer a state of resistance to viral infectivity at one or more stages of virus entry or replication. These biological effects require binding to the type I IFN receptor complex, which is composed of two subunits, ␣ and ␤ (12). Both subunits undergo rapid ligand-dependent tyrosine phosphorylation, and the ␣ subunit itself acts as a species-specific transducer for type I IFN action (7). At least 30 genes are known to be transcriptionally induced by type I IFNs, including 2Ј,5Ј-oligoadenylate synthetase (2Ј5ЈOAS), the double-stranded RNA-activated protein kinase, and the IFN-I response factor I (8, 10). 2Ј5ЈOAS is important for antiviral response, and its activity is required by cells to activate the endonuclease RNase L, which degrades RNA (31).The currently available treatment for HCV with r-hIFN-␣ results in clearance of the virus in only 20% of patients. However, recent clinical trials have shown that a combination of r-hIFN-␣ and the antiviral drug ribavirin can increase the percentage of recovery up to 40% (9, 30). Although these results appear to be very promising, systemic injection of r-hIFN-␣ is associated with severe side effects, which worsen in combination with ribavirin, causing the withdrawal of 20% of patients from therapy.It is not clear why r-hIFN-␣ treatment is effective in only a minority of patients. One possible explanation has been postulated on the basis of association of specific HCV genotype and lack of sustained response. HCV proteins may block IFN-␣-induced antiviral polypeptides, t...

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“…In mice resistant and semiresistant to MHV-3, treatment with MAbs raised against IFN results in conversion from resistance to susceptibility (Lucchiari et al, 1992;Virdizier & Gresser, 1978). Treatment with IFN type 1 has been shown to prolong survival following MHV exposure, particularly when treatment is started prior to viral infection (Minagawa et al, 1987;Kato et al, 1986). Although the mechanisms for the protective effect of IFNs were not examined in these studies, the beneficial effects of IFN may have been due to either their antiviral or immune effects (Whitaker-Dowling & Younger, 1987;Borden, 1992;Grossberg, 1987;Staeheli, 1990;Samuel, 1987;Pestka & Langer, 1987).…”

Section: Discussionmentioning

confidence: 99%

A 2',5'-oligoadenylate analogue inhibits murine hepatitis virus strain 3 (MHV-3) replication in vitro but does not reduce MHV-3-related mortality or induction of procoagulant activity in susceptible mice

Fingerote

Cruz

Gorczynski

et al. 1995

Journal of General Virology

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Exposure of inbred mice to murine hepatitis virus strain 3 (MHV-3) causes a strain dependent spectrum of disease symptoms which correlates with induction of procoagulant activity (PCA) by macrophages. Previous studies have demonstrated a role for intefferons in resistance to MHV-3 infection. These cytokines have both antiviral and immunoregulatory effects which may be crucial for MHV-3 resistance. One of their antiviral effects is the ability to induce 2',5'-oligoadenylate (2-5A) synthetase leading to activation of the latent endoribonuclease RNase L. Once activated, RNase L degrades ssRNA thereby inhibiting viral-induced protein synthesis. These studies were undertaken to determine the effects of Oragen 0004 (Oragen), an RNase L activating 2-5A analogue, on MHV-3 replication and induction of PCA in vitro and on the course of MHV-3 infection in susceptible BALB/cJ mice in vivo. Oragen inhibited MHV-3 replication in peritoneal macrophages derived from resistant A/J and susceptible BALB/cJ mice in a dose-dependent fashion. Concentrations of Oragen greater than 110 lag/2 x 106 macrophages decreased viral replication by greater than 89% in peritoneal macrophages in vitro obtained from both BALB/cJ and A/J mice and by 86% in livers from MHV-3qnfected mice in vivo. However, Oragen failed to inhibit induction of PCA following in vitro exposure of BALB/cJ mice-derived peritoneal macrophages to MHV-3 and failed to prevent the development of fulminant hepatitis in BALB/cJ mice in vivo. Thus, these studies demonstrate clearly that induction of 2-5A synthase and inhibition of viral replication is not sufficient to prevent MHV-3-related hepatocellular injury, and these data further support the role of PCA in the pathogenesis of MHV-3 infection.

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Protective effect of recombinant murine interferon beta against mouse hepatitis virus infection

Cited by 25 publications

References 17 publications

Expression of Mig (Monokine Induced by Interferon-γ) Is Important in T Lymphocyte Recruitment and Host Defense Following Viral Infection of the Central Nervous System

Expression of Mig (Monokine Induced by Interferon-γ) Is Important in T Lymphocyte Recruitment and Host Defense Following Viral Infection of the Central Nervous System

Liver-Specific Alpha 2 Interferon Gene Expression Results in Protection from Induced Hepatitis

A 2',5'-oligoadenylate analogue inhibits murine hepatitis virus strain 3 (MHV-3) replication in vitro but does not reduce MHV-3-related mortality or induction of procoagulant activity in susceptible mice

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