Myocarditis Associated With Reovirus Infection

Terheggen, F.; Benedikz, Elizabeth Kristin; Frissen, P. H. J.; Brinkman, Kees

doi:10.1007/s10096-003-0884-8

Cited by 7 publications

(5 citation statements)

References 6 publications

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“…Depending on the reovirus strain the suckling mouse can be infected by injection to cause encephalitis [8,9] and myocarditis [10-12], and the oral route of infection has been shown to differ in effectiveness among reoviruses. In particular type1 strain Lang (T1L) and murine type 3 isolate Clone 9, can establish infection in suckling mice but not adult mice via the oral route [13-15], and high dosages of type 3 strain Dearing (T3D) are required for infection of mice via the oral route in both suckling and adult animals [16,17].…”

Section: Introductionmentioning

confidence: 99%

Respiratory infection of mice with mammalian reoviruses causes systemic infection with age and strain dependent pneumonia and encephalitis

Gauvin

Bennett

Liu

et al. 2013

Virol J

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BackgroundBecause mammalian reoviruses are isolated from the respiratory tract we modeled the natural history of respiratory infection of adult and suckling mice with T1 Lang (T1L) and T3 Dearing (T3D) reoviruses.MethodsAdult and suckling Balb/c mice were infected by the intranasal route and were assessed for dose response of disease as well as viral replication in the lung and other organs. Viral antigen was assessed by immunofluorescence and HRP staining of tissue sections and histopathology was assessed on formalin fixed, H + E stained tissue sections.ResultsIntranasal infection of adult mice resulted in fatal respiratory distress for high doses (107 pfu) of T1L but not T3D. In contrast both T1L and T3D killed suckling mice at moderate viral dosages (105 pfu) but differed in clinical symptoms where T1L induced respiratory failure and T3D caused encephalitis. Infections caused transient viremia that resulted in spread to peripheral tissues where disease correlated with virus replication, and pathology. Immunofluorescent staining of viral antigens in the lung showed reovirus infection was primarily associated with alveoli with lesser involvement of bronchiolar epithelium. Immunofluorescent and HRP staining of viral antigens in brain showed infection of neurons by T3D and glial cells by T1L.ConclusionsThese mouse models of reovirus respiratory infection demonstrated age and strain dependent disease that are expected to be relevant to understanding and modulating natural and therapeutic reovirus infections in humans.

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Section: Introductionmentioning

confidence: 99%

Respiratory infection of mice with mammalian reoviruses causes systemic infection with age and strain dependent pneumonia and encephalitis

Gauvin

Bennett

Liu

et al. 2013

Virol J

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“…Even though WT reovirus infection is often asymptomatic or causes only mild disease in immunocompetent hosts, it can induce various pathologic manifestations, such as myocarditis, vasculitis, black tail syndrome and neuronal damage in newborn and immunodeficient animals (Sabin, 1959; Weiner et al , 1977; Baty and Sherry, 1993; Terheggen et al , 2003; DeBiasi et al , 2004; Loken et al , 2004). Genetic reassortment studies of reovirus genes have implicated S1 in having a significant role in determining reovirus pathogenesis (Weiner et al , 1977, 1980; Haller et al , 1995).…”

Section: Resultsmentioning

confidence: 99%

“…As WT reovirus is known to cause myocarditis (Baty and Sherry, 1993; Terheggen et al , 2003), heart tissue was examined by hematoxylin and eosin staining, and analysed by immunohistochemistry. Mice treated with WT reovirus showed distinct signs of viral myocarditis, as severe cardiac muscle damage and massive lymphocytic infiltration were observed (Figure 5C).…”

Section: Resultsmentioning

confidence: 99%

“…However, in immunocompromised hosts, such as newborn and severe combined immunodeficiency (SCID) animals; wild-type reovirus shows significant pathogenicity, especially to neural and cardiac muscle tissues (Sabin, 1959; Weiner et al , 1977; Baty and Sherry, 1993; Loken et al , 2004). Occasionally, this pathogenesis is observed in immunocompetent hosts, but mainly at high viral loads (Hirasawa et al , 2003; Terheggen et al , 2003). Clinical trials have reported no severe toxicity when utilising wild-type reovirus in combination with radiation or chemotherapy (Thirukkumaran and Morris, 2009).…”

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Attenuated reovirus displays oncolysis with reduced host toxicity

et al. 2010

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Background:Although the naturally occurring reovirus causes only mild symptoms in humans, it shows considerable potential as an oncolytic agent because of its innate ability to target cancer cells. In immunocompromised hosts, however, wild-type reovirus can target healthy tissues, including heart, liver, pancreas and neural structures.Methods:We characterized an attenuated form of reovirus (AV) derived from a persistently infected cell line through sequence analysis, as well as western blot and in vitro transcription and translation techniques. To examine its pathogenesis and oncolytic potential, AV reovirus was tested on healthy embryonic stem cells, various non-transformed and transformed cell lines, and in severe combined immunodeficiency (SCID) mice with tumour xenografts.Results:Sequence analysis of AV reovirus revealed a premature STOP codon in its sigma 1 attachment protein. Western blot and in vitro translation confirmed the presence of a truncated σ1. In comparison to wild-type reovirus, AV reovirus did not kill healthy stem cells or induce black tail formation in SCID mice. However, it did retain its ability to target cancer cells and reduce tumour size.Conclusion:Despite containing a truncated attachment protein, AV reovirus still preferentially targets cancer cells, and compared with wild-type reovirus it shows reduced toxicity when administered to immunodeficient hosts, suggesting the potential use of AV reovirus in combination cancer therapy.

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“…As Ras gene mutations are frequently observed in various types of human cancers [7], these findings have led to the current use of reovirus in clinical trials [5,8]; however, in immunocompromised hosts, such as newborn and severe combined immunodeficiency (SCID) animals, the wild-type reovirus causes significant viral pathogenesis, especially in neural and cardiac muscle tissues [9][10][11][12]. In some cases, even in immunecompetent hosts, including humans, the wild-type reovirus has been associated with viral pathogenesis [13,14]; therefore, especially in immunocompromised or very young hosts, the wild-type reovirus does not always act in a benign manner. We speculate that this concern might apply, in some cases, to cancer patients treated with extensive radio/chemotherapy, as they can…”

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confidence: 99%