The central interactive region of human MxA GTPase is involved in GTPase activation and interaction with viral target structures

Flohr, Felix; Schneider‐Schaulies, Sibylle; Haller, Otto; Kochs, Georg

doi:10.1016/s0014-5793(99)01598-7

Cited by 130 publications

(103 citation statements)

References 34 publications

(60 reference statements)

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“…In parallel, lung samples from RSV-infected animals were analysed for the expression of Mx proteins by Western blotting using monoclonal antibody M143 prepared against human MxA, which recognizes the N-terminal region of Mx proteins from most species, including mouse, rat and cotton rat (Flohr et al, 1999;Pletneva et al, 2006) (Fig. 1c).…”

Section: Rsv Infection Induces MX Proteins In Cotton Rat Lungsmentioning

confidence: 99%

Induction of type I interferons and interferon-inducible Mx genes during respiratory syncytial virus infection and reinfection in cotton rats

Pletneva¹,

Haller

Porter³

et al. 2008

Journal of General Virology

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Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis in young children. In general, RSV is considered to be a poor inducer of type I (alpha/beta) interferons (IFNs). Measurement of active type I IFN production during infection in vivo is demanding, as multiple IFN subtypes with overlapping activities are produced. In contrast, Mx gene expression, which is tightly regulated by type I IFN expression, is easily determined. This study therefore measured Mx expression as a reliable surrogate marker of type I IFN activity during RSV infection in vivo in a cotton rat model. It was shown that expression of Mx genes was dramatically augmented in the lungs of infected animals in a dose- and virus strain-dependent manner. The expression of Mx genes in the lungs was paralleled by their induction in the nose and spleen, although in spleen no simultaneous virus gene expression was detected. Reinfection of RSV-immune animals leads to abortive virus replication in the lungs. Thus, type I IFN and Mx gene expression was triggered in reinfected animals, even though virus could not be isolated from their lungs. Furthermore, it was demonstrated that immunity to RSV wanes with time. Virus replication and Mx gene expression became more prominent with increasing intervals between primary infection and reinfection. These results highlight the role of type I IFN in modulation of the immune response to RSV.

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Section: Rsv Infection Induces MX Proteins In Cotton Rat Lungsmentioning

confidence: 99%

Induction of type I interferons and interferon-inducible Mx genes during respiratory syncytial virus infection and reinfection in cotton rats

Pletneva¹,

Haller

Porter³

et al. 2008

Journal of General Virology

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“…To detect MxA and b-tubulin, the blots were incubated with monoclonal mouse antibodies directed against MxA (M143, [Flohr et al, 1999] and b-tubulin (131B, Sigma, Munich, Germany). Horseradish peroxidase-labeled antibodies and the ECL system (Amersham Pharmacia) were used to detect the primary antibodies.…”

Section: Western Blot Analysismentioning

confidence: 99%

Rapid and simple detection of IFN‐neutralizing antibodies in chronic hepatitis C non‐responsive to IFN‐α

Jorns

Holzinger

Thimme

et al. 2005

Journal of Medical Virology

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Different mechanisms have been proposed for the failure of interferon (IFN) therapy in patients with chronic hepatitis C and multiple sclerosis, for example, the presence of IFN-neutralizing antibodies. In this study, a novel assay system based on the IFN-inducible Mx-promoter was used to detect IFN-neutralizing antibodies in sera of patients with chronic hepatitis C. To monitor IFN bioactivity in IFN-treated patients, a real-time RT-PCR for MxA gene expression in PBMCs was established. Using these two methods, patients with chronic hepatitis C virus (HCV) infection receiving IFN therapy and patients with treatment induced HCV clearance were monitored. Importantly, neutralizing anti-IFN antibodies were detected in the sera of 3 of 38 chronically HCVinfected patients who failed to respond to therapy but none in sera of patients who cleared HCV after IFN therapy. Interestingly, the presence of these antibodies correlated with the lack of MxA induction in PBMCs after initiation of IFN-a therapy. Retrospective analysis of one patient's sera revealed that the anti-IFN-a antibodies had already developed after the first of four unsuccessful IFN therapies, suggesting that neutralizing antibodies may have contributed to the failure of previous IFN treatments. In summary, a novel screening assay was established that may be helpful for testing IFN non-responders for the presence of clinically relevant anti-IFN-a antibodies and for selecting alternative IFN preparations not neutralized by these antibodies.

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“…After blocking endogenous peroxidase with 0.1% H 2 O 2 in PBS for 20 min, sections were incubated with 10% normal rabbit serum for 1 h and then overnight at 4°C with anti-BDCA2 mAb (Miltenyi Biotec) and anti-CD123 (IL-3R␣) mAb (BD Biosciences) diluted 1/15 and 1/100 in PBS, respectively, or anti-CD3 mAb (Immunotech, Marseille, France). For MxA immunostaining, sections were incubated for 1 h at room temperature with anti-MxA mAb (clone M143, courtesy of Dr. O. Haller, Abteilung Virologie, Institute fur Medizinische Mikrobiologie und Hygiene, Universitat Freiburg, Freiburg, Germany) diluted 1/400 in PBS containing 2% BSA (18). The binding of biotinylated secondary Ab (rabbit anti-mouse IgG from The Jackson Laboratory, Bar Harbor, ME) was visualized with the avidin-biotin-HRP complex technique (ABC Vectastain Elite kit; Vector Laboratories, Burlingame, CA) and 3,3Ј-diaminobenzidine (Sigma-Aldrich) as substrate.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Characterization and Recruitment of Plasmacytoid Dendritic Cells in Synovial Fluid and Tissue of Patients with Chronic Inflammatory Arthritis

Lande¹,

Giacomini²,

Serafini

et al. 2004

The Journal of Immunology

138

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Dendritic cells (DCs) are thought to play a key role in driving the immunopathogenic response underlying chronic inflammatory arthritis. In this study, we have examined the presence and phenotype of plasmacytoid DCs (pDCs) in the synovial fluids (SF) of patients with rheumatoid arthritis (RA), psoriatic arthritis (PA), and osteoarthritis (OA) and determined the chemotactic properties of SF from these patients toward pDCs. Flow cytometry analysis showed that the percentage of pDCs, identified as a population of Lin−CD123++ cells, is 4- to 5-fold higher in RA SF and PA SF than in OA SF. The morphological and immunophenotypic characterization of pDCs isolated from PA and RA SF indicates that they are in an immature state, most likely due to inhibitory factors present in RA SF, but are still able to undergo maturation when exposed ex vivo to viral agent or unmethylated DNA. CD123+ and BDCA2+ pDCs were detected by immunohistochemistry in RA synovial tissue in which expression of the IFN-α-inducible protein MxA was also found, suggesting production of type I IFN by maturing pDCs. We also show that CXCR3 and CXCR4 are expressed by both blood-derived pDCs and pDCs isolated from RA and PA SF and that CXCL-10, CXCL-11, and CXCL-12 present in RA and PA SF stimulate chemotaxis of blood-derived pDCs. Altogether, these findings suggest that chemokine-driven recruitment of pDCs from the blood to the inflamed synovium could be important in the regulation of the immune response in chronic inflammatory arthritis.

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The central interactive region of human MxA GTPase is involved in GTPase activation and interaction with viral target structures

Cited by 130 publications

References 34 publications

Induction of type I interferons and interferon-inducible Mx genes during respiratory syncytial virus infection and reinfection in cotton rats

Induction of type I interferons and interferon-inducible Mx genes during respiratory syncytial virus infection and reinfection in cotton rats

Rapid and simple detection of IFN‐neutralizing antibodies in chronic hepatitis C non‐responsive to IFN‐α

Characterization and Recruitment of Plasmacytoid Dendritic Cells in Synovial Fluid and Tissue of Patients with Chronic Inflammatory Arthritis

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