Disease relevance of MX1

• The conclusion that resistance to influenza virus and vesicular stomatitis virus was due to the specific action of MxA is further supported by the observation that transfected 3T3 cell lines expressing the related MxB failed to acquire virus resistance [1].
• Surprisingly, MxA also conferred resistance to vesicular stomatitis virus [1].
• In this report we show that transfected cell lines expressing MxA acquired a high degree of resistance to influenza A virus [1].
• Expression of MxA in transfected 3T3 cells had no effect on the multiplication of two picornaviruses, a togavirus, or herpes simplex virus type 1 [1].
• Among them, myxovirus resistance protein A (MxA) appears to have the highest specificity, but it has no role in the pathogenesis of multiple sclerosis (MS) [2].

Psychiatry related information on MX1

• The localization of alpha-interferon (alpha-IFN) and its induced protein, MxA, was examined in human brain tissues from neurologically normal, Alzheimer's disease (AD) and Parkinson's disease (PD) cases [3].

High impact information on MX1

• This activation results not only in increased antigen presentation and T cell stimulatory capacity, but also in resistance to the cytopathic effect of the virus, mediated by the production of type I interferon, and upregulation of MxA [4].
• Forced expression of MxA in Hep3B cells enhances their sensitivity to mitomycin C and induces apoptosis, similar to the FA phenotype [5].
• MxA overexpression reveals a common genetic link in four Fanconi anemia complementation groups [5].
• Our results thus define an MxA region that determines antiviral specificity and further demonstrate that nuclear forms of MxA can mimic the action of mouse Mx1 whose natural location is the cell nucleus [6].
• Haplotype frequencies of the MX1 locus of chromosome 21 distinguish Koyas and Chenchus, along with Indian caste groups, from European and eastern Asian populations [7].

Chemical compound and disease context of MX1

• We infected human alveolar epithelium-like A549 cells and fibroblast-like human fetal lung (HFL1) cells with a pathogenic influenza A virus (A/Beijing/353/89), and studied the kinetics of infection and the expression of host IFN-alpha/beta, MxA, OAS (2',5'-oligoadenylate synthetase), and HLA class I and II genes [8].
• Antiviral effects of geranylgeranylacetone: enhancement of MxA expression and phosphorylation of PKR during influenza virus infection [9].
• The influence of tumor temperature (28, 32, 37, 39, 41, or 43 degrees C for 1 h) on the therapeutic efficacy of i.v. single bolus injections of ifosfamide (IFO) (32, 65, 125, or 250 mg/kg body weight) in human tumor xenografts (MX1 breast carcinoma) grown in nude mice (n = 240) was studied [10].
• 4-DM-PEN was demonstrated to be an antitumor-active metabolite of penclomedine in vivo when evaluated against the penclomedine-sensitive MX-1 human breast tumor xenograft implanted either s.c. or intracerebrally and is believed to be on the metabolic activation pathway of penclomedine [11].
• Concomitant Aminosyn treatment did not alter the efficacy of acivicin in mice bearing L1210 leukemia or MX-1 human mammary carcinoma [12].

Biological context of MX1

• A minimum tiling path (MTP) was subsequently defined that consists of 20 PACs, 2 BACs, and 5 cosmids covering 3 Mb between D21S3 and MX1 [13].
• Treatment of MxA-expressing cells with antibodies to mouse alpha-beta interferon did not abolish the resistance phenotype [1].
• We observed that in HepG2 and HuH7 cells IFN-inducible genes were upregulated by IFNs, but relatively high concentrations of IFN-alpha were needed to turn on MxA (an antiviral gene) and MxB gene expression [14].
• METHODS: HepG2 cells were transfected with the plasmid pHCV-Co, and, after treatment with IFN-alpha , levels of MxA, protein kinase R (PKR), and 2'-5' oligoadenylate synthetase (2'-5'OAS) mRNA were determined [15].
• RESULTS: Levels of MxA mRNA in pHCV-Co-transfected cells decreased in a dose-dependent manner, by down-regulation of the MxA gene promoter [15].

Anatomical context of MX1

• The IFN-induced MxA protein was detected in the IFN-treated Vero cells [16].
• In contrast, IFN-alpha 8 did not affect T cell motility, despite having similar antiviral properties and similar effects on the induction of the antiviral protein MxA [17].
• We demonstrate for the first time that MxA self-assembles into rings that tubulate lipids in vitro, and associates with a specific membrane compartment in cells, the smooth endoplasmic reticulum [18].
• Regulation of IFN-alpha/beta, MxA, 2',5'-oligoadenylate synthetase, and HLA gene expression in influenza A-infected human lung epithelial cells [8].
• Analysis of MxA protein in lymphocytes together with analysis of NAb is a promising marker for evaluating the biologic effects of IFNbeta treatment in MS patients [19].

Associations of MX1 with chemical compounds

• Substitutions were made for highly conserved arginine residues in either the LLP-1 or LLP-2 domain (MX1 or MX2, respectively) or in both domains (MX4) [20].
• MxA protein is a member of the dynamin superfamily of large guanosine triphosphatases [21].
• It is concluded that pretreatment hepatocellular MxA expression may become a useful predictor of response to combination treatment with IFN-alpha and ribavirin [22].
• Using cisplatin and a new porphyrin-derived compound TMPyP4, we showed that our model was able to detect a down-regulation of the telomerase activity in MCF7 cells in culture and in a human MX1 tumour xenografts [23].
• Tumor growth delays were obtained in the MX1 human breast carcinoma xenograft treated with various combinations of Adriamycin (doxorubicin), Fluosol-DA, and carbogen breathing (95% oxygen/5% carbon dioxide) [24].

Physical interactions of MX1

• Using a yeast two-hybrid interaction assay, we found that the second ankyrin-like repeat domain of TRPC6 interacted with MxA, a member of the dynamin superfamily [25].
• We studied prospectively the induction of MxA protein and the development of binding (BAb) and neutralising antibodies (NAb) in nine relapsing-remitting MS (RRMS) patients during one year of intramuscular IFNbeta -1a (Avonex((R))) treatment [26].

Regulatory relationships of MX1

• RESULTS: Pretreatment of Huh-7 cells with 0.5-1 mM H2O2 resulted in the suppression of the IFN-alpha-induced antiviral protein MxA and of IRF-9 mRNA expression [27].
• Additionally, we showed IL-28A and IL-29 induced reporter genes--protein MxA promoter linked to luciferase, or interferon stimulated response element (ISRE) linked to secreted alkaline phosphatase (SEAP)--more weakly than IFN [28].
• The addition of antibodies to beta interferon (IFN-beta) blocked interferon-directed MxA induction by >90% and demonstrated that hantavirus infection induces the secretion of IFN-beta from endothelial cells [29].
• The present findings are consistent with previous data which indicated that cytoplasmic MxA prevents transport of vRNPs into the nucleus, whereas nuclear MxA directly inhibits the viral polymerase activity in the nucleus [30].

Other interactions of MX1

• Chloramphenycol acethyl transferase (CAT) analysis was performed on cells cotransfected with pHCV-Co and pMx4CAT (containing the MxA gene promoter) and treated with IFN [15].
• Polymorphisms in the interferon-induced genes, MxA, OAS-1 and PKR appear thus associated with HCV outcome [31].
• This article describes a bioassay based on the real time PCR measurement of mRNA that results from the induction, in cultured human cells, of the MxA gene by IFNbeta [32].
• In addition, the assay was robust with respect to number of cells plated (i.e., increasing cell densities from 12x10(3)/well to 384x10(3)/well resulted in 3.03% variability in MxA expression normalized with glyceraldehyde-3 phosphate dehydrogenase) [32].
• Biological markers of interferon-beta therapy: comparison among interferon-stimulated genes MxA, TRAIL and XAF-1 [2].

Analytical, diagnostic and therapeutic context of MX1

• There are two commonly employed types of bioassays for the detection of neutralizing antibodies (NAbs) against interferon-beta (IFNbeta): the cytopatic effect assay (CPE), and the MxA (myxovirus resistance protein A) protein assay (MPA) [32].
• In influenza A virus-infected A549 and HFL1 cells, MxA gene induction was mediated by IFN-alpha/beta released into the cell culture supernatant, and was prevented by anti-type I IFN Abs [8].
• We show that recombinant MxA protein assembles into long filamentous structures with a diameter of about 20 nm at physiological salt concentration as demonstrated by sedimentation assays and electron microscopy [33].
• Levels of the antiviral protein MxA and soluble vascular cell adhesion molecule-1 (sVCAM) in the four groups were measured by ELISA [34].
• METHODS: The authors measured MxA in whole blood by ELISA, and serum-binding antibodies (SBA) by Western blot and ELISA in 134 samples of MS patients on IFNbeta-1b and 54 control subjects, and correlated the MxA levels and SBA titers with the NAB titer [35].

References