Effects of Type I Interferons on Friend Retrovirus Infection

Gerlach, Nicole; Schimmer, Simone; Weiß, Siegfried; Kalinke, Ulrich; Dittmer, Ulf

doi:10.1128/jvi.80.7.3438-3444.2006

Cited by 54 publications

(66 citation statements)

References 41 publications

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“…VSV infection induced similar IFN-␣ serum responses in WT and IFN-␤ Ϫ/Ϫ mice. This is in line with previous findings that upon infection with VSV, Sindbis virus, or Friend virus, IFN-␣ induction was independent of IFN-␤ (6,28,29).…”

Section: Discussionsupporting

confidence: 81%

Upon Intranasal Vesicular Stomatitis Virus Infection, Astrocytes in the Olfactory Bulb Are Important Interferon Beta Producers That Protect from Lethal Encephalitis

Detje

Lienenklaus

Chhatbar

et al. 2015

J Virol

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Previously we found that following intranasal (i.n.) infection with neurotropic vesicular stomatitis virus (VSV) type I interferon receptor (IFNAR) triggering of neuroectodermal cells was critically IMPORTANCEThe central nervous system has long been considered an immune privileged site. More recently, it became evident that specialized immune mechanisms are active within the brain to control pathogens. Previously, we showed that virus, which entered the brain via the olfactory route, was arrested within the olfactory bulb by a type I IFN-dependent mechanism. Since peripheral type I IFN would not readily cross the blood-brain barrier and within the brain thus far no abundant type I IFN responses have been detected, here we addressed from where locally active IFN originated from. We found that upon intranasal VSV instillation, primarily astrocytes, and to a lesser extent neurons, were stimulated within the olfactory bulb to mount IFN-␤ responses that also activated and protected distal brain areas. Our results are surprising because in other infection models astrocytes have not yet been identified as major type I IFN producers.

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Section: Discussionsupporting

confidence: 81%

Upon Intranasal Vesicular Stomatitis Virus Infection, Astrocytes in the Olfactory Bulb Are Important Interferon Beta Producers That Protect from Lethal Encephalitis

Detje

Lienenklaus

Chhatbar

et al. 2015

J Virol

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“…As predicted from this model, IFN-␤-deficient mice exhibited greatly enhanced susceptibility to intranasal challenge with vaccinia virus (4). IFN-␤-deficient mice were also more susceptible to coxsackievirus B3 (5) and Friend retrovirus (11) infections. However, IFN-␤-deficient and wild-type mice were equally susceptible to intravenous challenge with vesicular stomatitis virus (1), which is highly lethal for mice lacking functional type I IFN receptors (25).…”

mentioning

confidence: 70%

Protective Role of Beta Interferon in Host Defense against Influenza A Virus

Koerner

Kochs

Kalinke

et al. 2007

J Virol

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166

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Type I interferon (IFN), which includes the IFN-␣ and -␤ subtypes, plays an essential role in host defense against influenza A virus. However, the relative contribution of IFN-␤ remains unresolved. In mice, type I IFN is effective against influenza viruses only if the IFN-induced resistance factor Mx1 is present, though most inbred mouse strains, including the recently developed IFN-␤-deficient mice, bear only defective Mx1 alleles. We therefore generated IFN-␤-deficient mice carrying functional Mx1 alleles (designated Mx-BKO) and compared them to either wild-type mice bearing functional copies of both IFN-␤ and Mx1 (designated Mx-wt) or mice carrying functional Mx1 alleles but lacking functional type I IFN receptors (designated Mx-IFNAR). Influenza A virus strain SC35M (H7N7) grew to high titers and readily formed plaques in monolayers of Mx-BKO and Mx-IFNAR embryo fibroblasts which showed no spontaneous expression of Mx1. In contrast, Mx-wt embryo fibroblasts were found to constitutively express Mx1, most likely explaining why SC35M did not grow to high titers and formed no visible plaques in such cells. In vivo challenge experiments in which SC35M was applied via the intranasal route showed that the 50% lethal dose was about 20-fold lower in Mx-BKO mice than in Mx-wt mice and that virus titers in the lungs were increased in Mx-BKO mice. The resistance of Mx-BKO mice to influenza A virus strain PR/8/34 (H1N1) was also substantially reduced, demonstrating that IFN-␤ plays an important role in the defense against influenza A virus that cannot be compensated for by IFN-␣.Type I interferon (IFN) plays a key role in the innate immune response against many viruses (12). In addition, it further shapes the adaptive immune response against viral and nonviral pathogens (3). In the mouse, type I IFN comprises 14 IFN-␣ isoforms and a single form of IFN-␤ (28). Virus-induced synthesis of type I IFN in fibroblasts is hierarchical, with IFN-␤ appearing first, followed by IFN-␣ in a second wave (7,17). Studies with primary fibroblasts of mice with a targeted deletion of the IFN-␤ gene largely confirmed the view that IFN-␤ serves as immediate-early IFN (21).If the model of hierarchical organization of type I IFN expression observed in fibroblasts is maintained in the critical cell types of the intact organism, IFN-␤-deficient mice should exhibit enhanced susceptibility to virus infections. As predicted from this model, IFN-␤-deficient mice exhibited greatly enhanced susceptibility to intranasal challenge with vaccinia virus (4). IFN-␤-deficient mice were also more susceptible to coxsackievirus B3 (5) and Friend retrovirus (11) infections. However, IFN-␤-deficient and wild-type mice were equally susceptible to intravenous challenge with vesicular stomatitis virus (1), which is highly lethal for mice lacking functional type I IFN receptors (25). Furthermore, wild-type and IFN-␤-deficient mice did not differ significantly in susceptibility to La Crosse virus (G. Blakqori, S. Delhaye, S. Haid, M. Habjan, U. Kalinke, S. Weiss, T. M...

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“…In SIV infections, a transient peak of IFN-a was detectable in the blood and lymph nodes of rhesus macaques, but the viral burden was not significantly suppressed by the IFN-a levels (28). In previous studies of our group we could show that during FV infection of mice, IFN-a protein was not detectable in the serum (29,30). It was also found in in vitro studies that specific DC subsets can activate HIV-specific T cells by the induction of type I IFN or IL-12p70 (31), and a stimulation with the TLR3/MDA5 ligand polyinosinic-polycytidylic acid [poly (I:C)] can inhibit HIV replication in vitro, which is mediated by type I IFNs (32).…”

mentioning

confidence: 85%

“…Differences between the untreated control group (FV) and the group of treated mice [FV + poly(I:C)] were analyzed by using the unpaired Student t test. Statistically significant differences between the groups are indicated as follows: ppp , 0.005; pppp , 0.0005. cation in vitro and in vivo (29). Therefore, we wanted to analyze whether poly(I:C), which is known to be an effective inducer of type I IFN (40), can modulate FV infection in vivo.…”

Section: Poly(i:c) Induced Ifn-a In Fv-infected Animalsmentioning

confidence: 99%

Polyinosinic-Polycytidylic Acid Treatment of Friend Retrovirus-Infected Mice Improves Functional Properties of Virus-Specific T Cells and Prevents Virus-Induced Disease

Gibbert

Dietze

Zelinskyy

et al. 2010

The Journal of Immunology

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The induction of type I IFN is the most immediate host response to viral infections. Type I IFN has a direct antiviral activity mediated by antiviral enzymes, but it also modulates the function of cells of the adaptive immune system. Many viruses can suppress type I IFN production, and in retroviral infections, the initial type I IFN is weak. Thus, one strategy of immunotherapy in viral infection is the exogenous induction of type I IFN during acute viral infection by TLR ligands. Along these lines, the TLR3/MDA5 ligand polyinosinic-polycytidylic acid [poly(I:C)] has already been used to treat viral infections. However, the immunological mechanisms underlying this successful therapy have not been defined until now. In this study, the Friend retrovirus (FV) mouse model was used to investigate the mode of action of poly(I:C) in antiretroviral immunotherapy. Postexposure, poly(I:C) treatment of FV-infected mice resulted in a significant reduction in viral loads and protection from virus-induced leukemia. This effect was IFN dependent because type I IFN receptor-deficient mice could not be protected by poly(I:C). The poly(I:C)-induced IFN response resulted in the expression of antiviral enzymes, which suppressed FV replication. Also, the virus-specific T cell response was augmented. Interestingly, it did not enhance the number of virus-specific CD4+ and CD8+ T cells, but rather the functional properties of these cells, such as cytokine production and cytotoxic activity. The results demonstrate a direct antiviral and immunomodulatory effect of poly(I:C) and, therefore, suggests its potential for clinical treatment of retroviral infections.

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Effects of Type I Interferons on Friend Retrovirus Infection

Cited by 54 publications

References 41 publications

Upon Intranasal Vesicular Stomatitis Virus Infection, Astrocytes in the Olfactory Bulb Are Important Interferon Beta Producers That Protect from Lethal Encephalitis

Upon Intranasal Vesicular Stomatitis Virus Infection, Astrocytes in the Olfactory Bulb Are Important Interferon Beta Producers That Protect from Lethal Encephalitis

Protective Role of Beta Interferon in Host Defense against Influenza A Virus

Polyinosinic-Polycytidylic Acid Treatment of Friend Retrovirus-Infected Mice Improves Functional Properties of Virus-Specific T Cells and Prevents Virus-Induced Disease

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