Type I Interferons and IRF-1 Play a Critical Role in the Control of a Gammaherpesvirus Infection

Dutia, Bernadette M.; Allen, Deborah; Dyson, Heather; Nash, Anthony

doi:10.1006/viro.1999.9834

Cited by 87 publications

(91 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alternatively, an increased activity of CD4 ϩ CD25 ϩ T regulatory cells following infection might have also suggested that such a host response was necessary to limit viral-induced pathophysiology. This too would have been consistent with our understanding of ␥HV-68 pathology, which routinely resolves itself in normal mice, but can be greatly exacerbated in mice which have immune defects (45,46). Surprisingly, we found that the levels of FoxP3 mRNA ( Figs.…”

Section: Discussionsupporting

confidence: 69%

Murine γ-Herpesvirus 68 Limits Naturally Occurring CD4+CD25+ T Regulatory Cell Activity following Infection

Gasper-Smith

Marriott

Bost

2006

The Journal of Immunology

View full text Add to dashboard Cite

During microbial infections, naturally occurring CD4+CD25+ T regulatory cells can suppress protective host responses or they can limit pathogen-induced inflammatory responses. The particular role played by these cells seems to depend upon the infectious agent being investigated. γ-Herpesviruses are efficacious pathogens which are well-known for their ability to induce lymphoproliferative disease and to establish latency in the host. However, no studies have investigated the importance of naturally occurring CD4+CD25+ T regulatory cells during infection with these viruses. Using the murine model of γ-herpesvirus infection, murine γ-herpesvirus 68 (γHV-68), we were surprised to find that levels of the CD4+CD25+ T regulatory cell transcript, FoxP3, continued to decrease as viral latency increased and as the leukocytosis phase of the disease progressed. Consistent with these results, the decrease in FoxP3 protein expression followed similar kinetics. Along with the reduced expression of this regulatory T cell marker, we also observed diminished CD4+CD25+ T regulatory cell activity in these cells isolated from γHV-68-infected animals. Dendritic cells infected in vitro with γHV-68 did not alter the ability of normal CD4+CD25+ regulatory T cells to limit the proliferation of CD4+ Th cells following stimulation. Taken together, these studies demonstrate a decreased presence and activity of CD4+CD25+ T regulatory cells during the mononucleosis-like phase of this viral infection. These alterations in naturally occurring T regulatory cell function may help to explain the dysregulation of the host’s immune response which allows the uncontrolled expansion of leukocytes as viral latency is established.

show abstract

Section: Discussionsupporting

confidence: 69%

Murine γ-Herpesvirus 68 Limits Naturally Occurring CD4+CD25+ T Regulatory Cell Activity following Infection

Gasper-Smith

Marriott

Bost

2006

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…For example, ifnar −/− mice are very sensitive to VSV infection, whereas ifngr −/− mice are resistant (1). Immune-mediated inhibition of acute MHV-68 infection also requires type I but not type II IFNs (18,19).…”

Section: Discussionmentioning

confidence: 99%

Systematic identification of type I and type II interferon-induced antiviral factors

Liu

Sanchez

Aliyari

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

410

377

View full text Add to dashboard Cite

Type I and type II interferons (IFNs) are cytokines that establish the cellular antiviral state through the induction of IFN-stimulated genes (ISGs). We sought to understand the basis of the antiviral activity induced by type I and II IFNs in relation to the functions of their ISGs. Based on gene expression studies, we systematically identified antiviral ISGs by performing blinded, functional screens on 288 type I and type II ISGs. We assessed and validated the antiviral activity of these ISGs against an RNA virus, vesicular stomatitis virus (VSV), and a DNA virus, murine gammaherpes virus (MHV-68). Overall, we identified 34 ISGs that elicited an antiviral effect on the replication of either one or both viruses. Fourteen ISGs have uncharacterized antiviral functions. We further defined ISGs that affect critical life-cycle processes in expression of VSV protein and MHV-68 immediate-early genes. Two previously undescribed antiviral ISGs, TAP1 and BMP2, were further validated. TAP1-deficient fibroblasts were more susceptible to VSV infection but less so to MHV-68 infection. On the other hand, exogenous BMP2 inhibits MHV-68 lytic growth but did not affect VSV growth. These results delineate common and distinct sets of type I and type II IFN-induced genes as well as identify unique ISGs that have either broad or specific antiviral effects on these viruses.

show abstract

“…Early IFN-␣/␤ production is critical for controlling acute viral infection (18), and it has been suggested that early chemokine production might also contribute to the protective host response. Such a suggestion is supported by the observation that the viral M3 gene encodes a soluble chemokine receptor (19,20) that can compete for chemokine binding (19).…”

Section: Urine ␥-Herpesvirus-68 (␥Hv-68)mentioning

confidence: 99%

Murine γ-Herpesvirus-68-Induced IL-12 Contributes to the Control of Latent Viral Burden, but Also Contributes to Viral-Mediated Leukocytosis

Elsawa

Bost

2004

The Journal of Immunology

View full text Add to dashboard Cite

Early IFN-α/β production, followed by the development of a viral-specific CTL response, are critical factors in limiting the level of murine γ-herpesvirus-68 (γHV-68) infection. Development of a long-lived CTL response requires T cell help, and these CTLs most likely function to limit the extent of infection following reactivation. The importance of IL-12 in the development and/or activity of Th1 cells and CTLs is well documented, and we investigated the kinetics and magnitude of γHV-68-induced IL-12 production. Following intranasal infection, IL-12 and IL-23 mRNA expression was up-regulated in lung and spleen and lung, respectively, followed by increased levels of IL-12p40 in lung homogenates and sera. Exposure of cultured macrophages or dendritic cells to γHV-68 induced secretion of IL-12, suggesting that these cells might be responsible for IL-12 production in vivo. γHV-68 infection of mice made genetically deficient in IL-12p40 expression (IL-12p40−/−) resulted in a leukocytosis and splenomegaly that was significantly less than that observed in syngeneic C57BL/6 mice. IL-12p40−/− mice showed increased levels of infectious virus in the lung, but only at day 9 postinfection. Increased levels of latent virus in the spleen at day 15 postinfection were also observed in IL-12p40−/− mice when compared with syngeneic C57BL/6 mice. An overall reduction in γHV-68-induced IFN-γ production was observed in IL-12p40−/− mice, suggesting that most of the viral-induced IFN-γ in C57BL/6 mice was IL-12 dependent. Taken together, these results suggest that γHV-68-induced IL-12 contributes to the pathophysiology of viral infection while also functioning to limit viral burden.

show abstract

Type I Interferons and IRF-1 Play a Critical Role in the Control of a Gammaherpesvirus Infection

Cited by 87 publications

References 30 publications

Murine γ-Herpesvirus 68 Limits Naturally Occurring CD4+CD25+ T Regulatory Cell Activity following Infection

Murine γ-Herpesvirus 68 Limits Naturally Occurring CD4+CD25+ T Regulatory Cell Activity following Infection

Systematic identification of type I and type II interferon-induced antiviral factors

Murine γ-Herpesvirus-68-Induced IL-12 Contributes to the Control of Latent Viral Burden, but Also Contributes to Viral-Mediated Leukocytosis

Contact Info

Product

Resources

About