Proinflammatory Effects of Interferon Gamma in Mouse Adenovirus 1 Myocarditis

McCarthy, Mary K.; Procario, Megan C.; Twisselmann, Nele; Wilkinson, John E.; Archambeau, Ashley; Michele, Daniel E.; Day, Sharlene M.; Weinberg, Jason B.

doi:10.1128/jvi.02077-14

Cited by 38 publications

(50 citation statements)

References 61 publications

(78 reference statements)

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“…It is possible that these differences could occur in an organ-specific manner. Consistent with that possibility, we have demonstrated that MAV-1-induced IFN-γ production is lower in the lungs of neonatal mice compared to adults (Procario et al, 2012), while IFN-γ production is substantially greater in hearts of infected neonates than in adults (McCarthy et al, 2015). …”

Section: Discussionsupporting

confidence: 80%

Prostaglandin E2 production during neonatal respiratory infection with mouse adenovirus type 1

et al. 2016

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Neonatal mice are more susceptible than adults to mouse adenovirus type 1 (MAV-1) respiratory infection. In adult mice, MAV-1 respiratory infection induces production of prostaglandin E2 (PGE2), a lipid mediator that exerts suppressive effects on a variety of host immune functions. We tested the hypothesis that exaggerated PGE2 production in neonatal mice contributes to increased susceptibility to MAV-1. PGE2 concentrations were lower in lungs of uninfected neonatal mice than in adults. PGE2 production was induced by both MAV-1 and a nonspecific stimulus to a greater degree in neonatal mice than in adults, but only in adults was PGE2 induced in a virus-specific manner. Lung viral loads were equivalent in PGE2-deficient neonatal mice and wild type controls, as was virus-induced expression of IFN-γ, IL-17A, and CCL5 in the lungs. PGE2 deficiency had minimal effect on production of virus-specific IgG or establishment of protective immunity in neonatal mice. Collectively, our data indicate that lung PGE2 production is exaggerated early in life, but this effect does not mediate increased susceptibility to MAV-1 infection.

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Section: Discussionsupporting

confidence: 80%

Prostaglandin E2 production during neonatal respiratory infection with mouse adenovirus type 1

et al. 2016

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“…Although IFN-γ does not exert a critical antiviral function during MAV-1 respiratory infection (Anderson et al, 2009; McCarthy et al, 2015b) or myocarditis (McCarthy et al, 2015a), we demonstrated that it is necessary for virus-induced inflammatory responses in the hearts of MAV-1-infected mice (McCarthy et al, 2015a). In the present study, we tested the hypothesis that IFN-γ-induced immunoproteasome activity is an important contributor to virus-induced inflammation.…”

Section: Introductionmentioning

confidence: 84%

“…We have used mouse adenovirus type 1 (MAV-1) to study the pathogenesis of adenovirus respiratory infection in its natural host (McCarthy et al, 2013; McCarthy et al, 2015b; McCarthy et al, 2014; Procario et al, 2012; Procario et al, 2016; Weinberg et al, 2005). Recently, we used MAV-1 to establish a mouse model of adenovirus myocarditis (McCarthy et al, 2015a) in which intranasal (i.n.) MAV-1 infection of neonatal C57BL/6 (B6) mice induces interferon gamma (IFN-γ) expression in the heart along with cellular inflammation, cardiac myocyte necrosis, and decreased cardiac contractility.…”

Section: Introductionmentioning

confidence: 99%

Interferon-dependent immunoproteasome activity during mouse adenovirus type 1 infection

et al. 2016

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The immunoproteasome is an inducible host mechanism that aids in the clearance of damaged proteins. The immunoproteasome also influences immune function by enhancing peptide presentation by MHC class I and promotes inflammation via IκB degradation and activation of NF-κB. We used mouse adenovirus type 1 (MAV-1) to characterize the role of the immunoproteasome in adenovirus pathogenesis. Following intranasal infection of mice, immunoproteasome activity in the heart and lung was significantly increased in an IFN-γ-dependent manner. Absence of the β5i immunoproteasome subunit and pharmacological inhibition of β5i activity had minimal effects on viral replication, virus-induced cellular inflammation, or induction of cytokine expression. Likewise, the establishment of protective immunity following primary infection was not significantly altered by β5i deficiency. Thus, although immunoproteasome activity is robustly induced during acute infection with MAV-1, our data suggest that other mechanisms are capable of compensating for immunoproteasome activity to maintain antiviral immunity and appropriate inflammatory responses.

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“…10). IFN-␥ is commonly produced by effector CD8 ϩ T lymphocytes, and upon recognition of the specific antigen, CTL activity can be measured (38,39). Several studies conducted in mice have demonstrated an important role for IFN-␥ in immune protection from herpesvirus infections (40,41).…”

Section: Figmentioning

confidence: 99%

Intramuscular Immunization of Mice with the Live-Attenuated Herpes Simplex Virus 1 Vaccine Strain VC2 Expressing Equine Herpesvirus 1 (EHV-1) Glycoprotein D Generates Anti-EHV-1 Immune Responses in Mice

Liu

Stanfield

Chouljenko

et al. 2017

J Virol

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Vaccination remains the best option to combat equine herpesvirus 1 (EHV-1) infection, and several different strategies of vaccination have been investigated and developed over the past few decades. Herein, we report that the liveattenuated herpes simplex virus 1 (HSV-1) VC2 vaccine strain, which has been shown to be unable to enter into neurons and establish latency in mice, can be utilized as a vector for the heterologous expression of EHV-1 glycoprotein D (gD) and that the intramuscular immunization of mice results in strong antiviral humoral and cellular immune responses. The VC2-EHV-1-gD recombinant virus was constructed by inserting an EHV-1 gD expression cassette under the control of the cytomegalovirus immediate early promoter into the VC2 vector in place of the HSV-1 thymidine kinase (UL23) gene. The vaccines were introduced into mice through intramuscular injection. Vaccination with both the VC2-EHV-1-gD vaccine and the commercially available vaccine Vetera EHV XP 1/4 (Vetera; Boehringer Ingelheim Vetmedica) resulted in the production of neutralizing antibodies, the levels of which were significantly higher in comparison to those in VC2-and mock-vaccinated animals (P Ͻ 0.01 or P Ͻ 0.001). Analysis of EHV-1-reactive IgG subtypes demonstrated that vaccination with the VC2-EHV-1-gD vaccine stimulated robust IgG1 and IgG2a antibodies after three vaccinations (P Ͻ 0.001). Interestingly, Vetera-vaccinated mice produced significantly higher levels of IgM than mice in the other groups before and after challenge (P Ͻ 0.01 or P Ͻ 0.05). Vaccination with VC2-EHV-1-gD stimulated strong cellular immune responses, characterized by the upregulation of both interferonand tumor necrosis factor-positive CD4 ϩ T cells and CD8 ϩ T cells. Overall, the data suggest that the HSV-1 VC2 vaccine strain may be used as a viral vector for the vaccination of horses as well as, potentially, for the vaccination of other economically important animals.IMPORTANCE A novel virus-vectored VC2-EHV-1-gD vaccine was constructed using the live-attenuated HSV-1 VC2 vaccine strain. This vaccine stimulated strong humoral and cellular immune responses in mice, suggesting that it could protect horses against EHV-1 infection.KEYWORDS EHV-1, HSV-1, equine herpesvirus, live vector vaccines, glycoprotein D, immune response, mouse model

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Proinflammatory Effects of Interferon Gamma in Mouse Adenovirus 1 Myocarditis

Cited by 38 publications

References 61 publications

Prostaglandin E2 production during neonatal respiratory infection with mouse adenovirus type 1

Prostaglandin E2 production during neonatal respiratory infection with mouse adenovirus type 1

Interferon-dependent immunoproteasome activity during mouse adenovirus type 1 infection

Intramuscular Immunization of Mice with the Live-Attenuated Herpes Simplex Virus 1 Vaccine Strain VC2 Expressing Equine Herpesvirus 1 (EHV-1) Glycoprotein D Generates Anti-EHV-1 Immune Responses in Mice

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