Type I interferon gene therapy protects against cytomegalovirus-induced myocarditis.
Journal: 2002/August - Immunology
ISSN: 0019-2805
PUBMED: 12100732
Abstract:
Type I interferons (IFNs) are produced early in response to viral infection and modulate adaptive immunity. Previously we demonstrated localized protection against murine cytomegalovirus (MCMV) infection in IFN DNA-inoculated mice. Here we examine the effect of seven IFN subtypes (IFNA1, A2, A4, A5, A6, A9 and B), administered by DNA inoculation, on systemic MCMV infection and myocarditis. IFN transgene expression altered the pathogenesis of MCMV infection with regard to virus titre and myocarditis. IFNA6 treatment reduced MCMV replication whilst IFNA5 and A2 enhanced virus replication. IFNA6, A9, and B treatment inhibited acute myocarditis. A T helper type 1-like, antibody and cytokine, response correlated with decreased virus titre and myocarditis. In addition, IFNA6 was able to reduce chronic cardiac inflammation. This research into the effectiveness of seven type I IFNs, using DNA gene therapy, highlights the need for correct subtype usage in the treatment of disease. We demonstrate effective subtypes for treatment in both the acute and chronic phases of MCMV infection and the resultant development of myocarditis.
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Immunology 106(3): 428-437

Type I interferon gene therapy protects against cytomegalovirus-induced myocarditis

Division of Veterinary and Biomedical Sciences, Murdoch University, Western Australian Biomedical Research Institute, Perth, Western Australia, Australia
Correspondence: Dr V. S. Cull, Division of Veterinary and Biomedical Sciences, Murdoch University, Perth, 6150, Australia. E-mail: ua.ude.hcodrum.tabmun@cassenav
Formerly Lawson.
Division of Veterinary and Biomedical Sciences, Murdoch University, Western Australian Biomedical Research Institute, Perth, Western Australia, Australia
Received 2001 Oct 31; Revised 2002 Feb 20; Accepted 2002 Feb 27.

Abstract

Type I interferons (IFNs) are produced early in response to viral infection and modulate adaptive immunity. Previously we demonstrated localized protection against murine cytomegalovirus (MCMV) infection in IFN DNA-inoculated mice. Here we examine the effect of seven IFN subtypes (IFNA1, A2, A4, A5, A6, A9 and B), administered by DNA inoculation, on systemic MCMV infection and myocarditis. IFN transgene expression altered the pathogenesis of MCMV infection with regard to virus titre and myocarditis. IFNA6 treatment reduced MCMV replication whilst IFNA5 and A2 enhanced virus replication. IFNA6, A9, and B treatment inhibited acute myocarditis. A T helper type 1-like, antibody and cytokine, response correlated with decreased virus titre and myocarditis. In addition, IFNA6 was able to reduce chronic cardiac inflammation. This research into the effectiveness of seven type I IFNs, using DNA gene therapy, highlights the need for correct subtype usage in the treatment of disease. We demonstrate effective subtypes for treatment in both the acute and chronic phases of MCMV infection and the resultant development of myocarditis.

Abstract

Acknowledgments

This work was supported by the Australian National Health and Medical Research Council (Project Grant 990393). We are especially grateful to VICAL for providing the pkCMVint mammalian expression vector.

Acknowledgments

Abbreviations

CMVcytomegalovirus
H & Ehaematoxylin & eosin
IEimmediate-early
IFNinterferon
MCMVmurine cytomegalovirus
p.i.post-infection
SEstandard error
TAtibialis anterior.
Abbreviations

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