Enhanced virus resistance of transgenic mice expressing the human MxA protein

Pavlovic, Jovan; Arzet, H A; Hefti, Hans Peter; Frese, Michael; Rost, Daniel; Ernst, Bernhard; Kolb, E.; Staeheli, Peter; Haller, Otto

doi:10.1128/jvi.69.7.4506-4510.1995

Cited by 116 publications

(45 citation statements)

References 45 publications

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“…DF-1 cells expressing duck RIG-I demonstrated a 33-fold increase in Mx1 expression in response to infection with BC500, and 21-fold by VN1203. The interferon-inducible Mx proteins confer antiviral function in transfected cells and transgenic animals (Engelhardt et al, 2004;Pavlovic et al, 1995;Pavlovic et al, 1990). In mice, Mx1 is interferon-induced and protects against lethal infection by the 1918 pandemic H1N1 strain and VN1203 (Tumpey et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Identification of avian RIG-I responsive genes during influenza infection

Barber

Aldridge

Fleming-Canepa

et al. 2013

Molecular Immunology

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Ducks can survive infection with highly pathogenic avian influenza viruses that are lethal to chickens. We showed that the influenza detector, RIG-I, can initiate antiviral responses in ducks, but this gene is absent in chickens. We can reconstitute this pathway by transfecting chicken DF-1 embryonic fibroblast cells with duck RIG-I, which augments their antiviral response to influenza and decreases viral titre. However, the genes downstream of duck RIG-I that mediate this antiviral response to influenza are not known. Using microarrays, we compared the transcriptional profile of chicken embryonic fibroblasts transfected with duck RIG-I or empty vector, and infected with low or highly pathogenic avian influenza viruses. Transfected duck RIG-I expressed in chicken cells was associated with the marked induction of many antiviral innate immune genes upon infection with both viruses. We used real-time PCR to confirm upregulation of a subset of these antiviral genes including MX1, PKR, IFIT5, OASL, IFNB, and downregulation of the influenza matrix gene. These results provide some insight into the genes induced by duck RIG-I upon influenza infection, and provide evidence that duck RIG-I can function to elicit an interferon-driven, antiviral response against influenza in chicken embryonic fibroblasts.

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Section: Discussionmentioning

confidence: 99%

Identification of avian RIG-I responsive genes during influenza infection

Barber

Aldridge

Fleming-Canepa

et al. 2013

Molecular Immunology

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“…Susceptible animals are equipped with the full armament of innate and adaptive immunity with the exception of Mx and resist all sorts of viruses but not orthomyxoviruses (Haller, 1981;Haller et al, 1998). Transgenic introduction of mouse or human Mx is sufficient to turn susceptible mice into resistant animals (Arnheiter et al, 1990;Pavlovic et al, 1995). More importantly, constitutive expression of human MxA in an otherwise IFN-non-responsive animal confers full protection, demonstrating the exquisite power of a single effector molecule of the human IFN system in an otherwise susceptible host (Hefti et al, 1999).…”

Section: The Amazing Power Of the Interferon Systemmentioning

confidence: 99%

“…Mx proteins belong to the superfamily of dynamin-like large GTPases and have been discovered as mediators of genetic resistance against orthomyxoviruses in mice. Their importance for host survival following infection with certain RNA viruses has been amply demonstrated (Arnheiter et al, 1996;Hefti et al, 1999;Pavlovic et al, 1995) but their exact mode of action is still unknown. The relevance of the OAS/RNaseL and PKR Fig.…”

Section: Ifn-stimulated Gene Products With Antiviral Activitymentioning

confidence: 99%

The interferon response circuit: Induction and suppression by pathogenic viruses

2006

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Type I interferons (IFN-alpha/beta) are potent antiviral cytokines and modulators of the adaptive immune system. They are induced by viral infection or by double-stranded RNA (dsRNA), a by-product of viral replication, and lead to the production of a broad range of antiviral proteins and immunoactive cytokines. Viruses, in turn, have evolved multiple strategies to counter the IFN system which would otherwise stop virus growth early in infection. Here we discuss the current view on the balancing act between virus-induced IFN responses and the viral counterplayers.

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“…In humans, two distinct Mx (MxA and MxB) are encoded on chromosome 21, while only MxA has exhibited antiviral activity (Sadler and Williams 2008). Transfected cells (Chieux et al 2001;Kochs and Haller 1999) and transgenic mice (Pavlovic et al 1995) overexpressing MxA acquire a high degree of antiviral resistance against several RNA viruses. In humans, synthesis of MxA protein is induced during viral infections and may protect humans from infection (Roers et al 1994;von Wussow et al 1990).…”

Section: Introductionmentioning

confidence: 99%

Association of functional polymorphisms in the MxA gene with susceptibility to enterovirus 71 infection

Zhang

Chen

et al. 2013

Hum Genet

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Myxovirus resistance A (MxA) is an antiviral protein induced by type I interferons α and β (IFN-α and IFN-β) that can inhibit virus replication. We examined whether the MxA polymorphisms were related to the risk and severity of enterovirus 71 (EV71) infection in Chinese populations. The MxA C-123A and G-88T polymorphisms were genotyped in two independent case-control populations in China by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). MxA messenger RNA was quantified by real-time quantitative PCR in peripheral blood mononuclear cells (PBMCs) from 45 healthy children and 19 patients with EV71 infection. Significantly decreased susceptibility to EV71 infection was observed for the -123A allele and -88T allele carriers, with ORs (95% CIs) estimated as 0.56 (0.39-0.81) and 0.64 (0.47-0.88), respectively, in the northern population. This association was confirmed in the southern population, with ORs (95% CIs) estimated as 0.58 (0.38-0.89) and 0.67(0.47-0.95), respectively. The A- 123T- 88 haplotype was also significantly associated with lower risk of EV71 infection in both the northern (OR = 0.62; 95% CI = 0.44-0.85) and the southern population (OR = 0.63; 95% CI = 0.43-0.92). Furthermore, we observed higher MxA messenger RNA levels in IFNβ1a-stimulated PBMCs from the -123A or -88T allele carriers compared with that from nocarriers. Our findings suggest that polymorphisms in the MxA promoter may play a role in mediating the susceptibility to EV71 infection in Chinese population.

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Enhanced virus resistance of transgenic mice expressing the human MxA protein

Cited by 116 publications

References 45 publications

Identification of avian RIG-I responsive genes during influenza infection

Identification of avian RIG-I responsive genes during influenza infection

The interferon response circuit: Induction and suppression by pathogenic viruses

Association of functional polymorphisms in the MxA gene with susceptibility to enterovirus 71 infection

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