MxA protein and its application in early diagnosis of viral infections including SARS-CoV-2
Authors:
M. Šrámková; P. Lehnert; R. Průša
Authors‘ workplace:
Ústav lékařské chemie a klinické biochemie 2. LF UK a FN Motol, Praha
Published in:
Klin. Biochem. Metab., 30, 2022, No. 3, p. 73-78
Overview
Myxovirus resistant proteins are closely related to interferons and their metabolic effects. MxA protein has direct antiviral activity, it is effective against both nuclear and cytoplasmic viruses. The localization of MxA in the cytoplasm and nucleus allows the targeting of viruses that can replicate in both compartments. Gene expression is strictly regulated exclusively by first and third type interferons. 76 kDa MxA belongs to the family of interferon-induced GTPases. MxA is used as a marker of viral diseases, as its concentration increases significantly due to viral infection as early as 1.2 hours and peaks after 16 hours. Qualitative determination of MxA is performed by a point-of-care lateral flow immunoassay or quantitative by ELISA. The clinical use of MxA has been described primarily in emergency departments and pediatrics, especially in patients with fever and symptoms of acute respiratory infection, including SARS-CoV-2. Determination of MxA protein in combination with CRP could be a valuable test for early diagnosis of viral infection and differentiation of bacterial infection. Decision limits vary depending on the used analytical method and the biological material being investigated.
Keywords:
interferon – myxovirus resistance protein – viral infections
Sources
1. Isaacs, A., Lindermann, J. Virus interference I: the interferon. Proc. Roy. Soc. London Ser. B, 1957, 147, 258 –267.
2. Schneider, W. M., Chevillotte, M. D., Rice, C. M. Interferon-stimulated genes: a complex web of host defenses. Annu. Rev. Immunol., 2014, 32, 513–545.
3. O‘Connell, R. M., Saha, S. K., Vaidya, S. A., Bruhn, K. W., Miranda, G. A., Zarnegar, B., Perry, A. K., Nguyen, B. O., Lane, T. F., Taniguchi, T., Miller, J. F., Cheng, G. Type I interferon production enhances susceptibility to Listeria monocytogenes infection. J. Exp. Med., 2004, 200, 437–445.
4. Jouanguy E, Zhang, S. Y., Chapgier, A., Sancho- Shimizu, V., Puel, A., Picard, C., Boisson-Dupuis, S,, Abel, L., Casanova, J. L. Human primary immunodeficiencies of type I interferons. Biochemie, 2007, 89, 878–883.
5. Makela, M. J., Puhakka, T., Ruuskanen, O., Leinonen, M., Saikku, P., Kimpimaki, M. Viruses and bacteria in the etiology of the common cold. J. Clin. Microbiol., 1998, 36, 539–542.
6. Libertínová, J., Kumstýřová, T., Meluzínová, E., Havrdová, E., Horáková, D., Kovářová, I., Hynčicová, E., Lišková, P., Houžvičková, E., Maťoška, V., Zajac, M., Tomek, A., Bojar, M., Marusič, P. mRNA MxA jako marker biologické účinnosti léčby interferonem-β u pacientů s RS v ČR. Cesk. Slov. Neurol. N., 2009, 72, 547–551.
7. Sadler, A. J., Williams, B. R. Interferon-inducible antiviral effectors. Nat Rev Immunol., 2008, 8, 559–568.
8. Petersen, M. B., Slaugenhaupt, S. A., Lewis, J. G., Warren, A. C., Chakravarti, A., Antonarakis, S. E. A genetic linkage map of 27 markers on human chromosome 21. Genomics, 1991, 9, 407–419.
9. Haller, O., Kochs, G. Human MxA protein: an interferoninduced dynamin like GTPase with broad antiviral aktivity. J. Interferon Cytokine Res., 2011, 31, 79–87.
10. Arnheiter, H., Haller, O. Antiviral state against influenza virus neutralized by microinjection of antibodies to interferon-induced Mx proteins. EMBO J., 1988, 7, 1315–1320.
11. Mibayashi, M., Nakad, K., Nagata, K. Promoted cell death of cells expressing human MxA by influenza virus infection. Microbiol. Immunol., 2002, 46, 29–36.
12. Mushinski, J. F., Nguyen, P., Stevens, L. M., Khanna, C., Lee, S., Chung, E. J., Lee, M. J., Kim, Y. S., Linehan, W. M., Horisberger, M. A., Trepel, J. B. Inhibition of tumor cell motility by the interferon-inducible GTPase MxA. J. Biol. Chem., 2009, 284, 15206–15214.
13. Tazi-Ahnini, R., di Giovine, F. S., McDonagh, A. J. G., Messenger, A. G., Amadou, C., Cox, A., Duff, G. W., Cork, M. J. Structure and polymorphism of the human gene for the interferon-induced p78 protein (MX1): evidence of association with alopecia areata in the Down syndrome region. Hum. Genet., 2000, 106, 639–645.
14. Aebi, M., Fäh, J., Hurt, N., Samuel, C. E., Thomis, D., Bazzigher, L., Pavlovic, J., Haller, O., Staeheli, P. CDNA structures and regulation of two interferoninduced human Mx proteins. Mol. Cell. Biol., 1989, 9, 5062–5072.
15. Haller, O., Frese, M., Rost, D., Nuttall, P. A., Kochs, G. Tick-borne thogoto virus infection in mice is inhibited by the orthomyxovirus resistance gene product Mx1. J. Virol., 1995, 69, 2596–2601.
16. Andersson, I., Bladh, L., Mousavi-Jazi, M., Magnusson, K. E., Lundkvist, A., Haller, O., & Mirazimi, A. Human MxA protein inhibits the replication of Crimean-Congo hemorrhagic fever virus. J. Virol., 2004, 78, 4323–4329.
17. Gordien, E., Rosmorduc, O., Peltekian, C., Garreau, F., Bréchot, C., Kremsdorf, D. Inhibition of hepatitis B virus replication by the interferon-inducible MxA protein. J. Virol., 2001, 75, 2684–2691.
18. MacQuillan, G. C., de Boer, W. B., Allan, J. E., Platten, M. A., Reed, W. D., Jeffrey, G. P. 2010. Hepatocellular MxA protein expression supports the differentiation of recurrent hepatitis C disease from acute cellular rejection after liver transplantation. Clin. Transplant., 2010, 24, 252–258.
19. Shaker, O., Ahmed, A., Doss, W., Abdel-Hamid, M. MxA expression as marker for assessing the therapeutic response in HCV genotype 4 Egyptian patients. J. Viral Hepat., 2010, 17, 794–799.
20. Low, H. H., Lowe, J. Dynamin architecture—from monomer to polymer. Curr. Opin. Struct. Biol. 2010, 20, 791–798.
21. Stertz, S., Reichelt, M., Krijnse-Locker, J., Mackenzie, J., Simpson, J. C., Haller, O., and Kochs, G. Interferon-induced, antiviral human MxA protein localizes to a distinct subcompartment of the smooth endoplasmic reticulum. J. Interferon Cytokine Res., 2006, 26, 650–660.
22. Miller, S., Krijnse-Locker, J. Modification of intracellular membrane structures for virus replication. Nat. Rev. Microbiol. 2008, 6, 363–374.
23. Accola, M. A., Huang, B., Masri, A. A., McNiven, M. A. The antiviral dynamin family member, MxA, tubulates lipids and localizes to the smooth endoplasmic reticulum. J. Biol. Chem., 2002, 277, 21829–21835.
24. Gao S, von der Malsburg, A., Paeschke, S., Behlke, J., Haller, O., Kochs, G., Daumke, O. Structural basis of oligomerisation in the stalk region of dynamin-like MxA. Nature, 2010, 465, 502– 506.
25. Kochs, G., Haller, O. Interferon-induced human MxA GTPase blocks nuclear import of Thogoto virus nucleocapsids. Proc. Natl. Acad. Sci. USA., 1999, 96, 2082–2086.
26. Beard, K., Chan, C., Mills, S., Poole, S., Brendish, N. J., Clark, T. W. Evaluation of the Febridx Host Response Point-of-Care Test to Differentiate Viral From Bacterial Aetiology in Adults Hospitalized with Acute Respiratory Illness During Influenza Season. Open Forum Infect. Dis., 2019, 6, S300–S301.
27. Clark, T. W., Brendish, N. J., Poole, S., Naidu, V. V., Mansbridge, C., Norton, N., Wheeler, H., Presland, L., Ewings, S. Diagnostic accuracy of the FebriDx host response point-of-care test in patients hospitalised with suspected COVID-19. J. Infect., 2020, 81, 607–613.
28. World Health Organization. (2015). Global action plan on antimicrobial resistance. World Health Organization. https://apps.who.int/iris/handle/10665 /193736
29. Cals, J. W., Hopstaken, R. M., Butler, C. C., Hood, K., Severens, J. L., Dinant, G. J. Improving management of patients with acute cough by C-reactive protein point of care testing and communication training (IMPAC3T): study protocol of a cluster randomised controlled trial. BMC Fam. Pract., 2007, 8, 15.
30. Gonzales, R., Bartlett, J. G., Besser, R. E., Cooper, R. J., Hickner, J. M., Hoffman, J. R., Sande, M. A. Principles of appropriate antibiotic use for treatment of nonspecific upper respiratory tract infections in adults: background, specific aims, and methods. Ann. Emerg. Med., 2001, 37, 690–697.
31. Nakabayashi, M., Adachi, Y., Itazawa, T., Okabe, Y., Kanegane, H., Kawamura, M. MxA-based recognition of viral illness in febrile children by a whole blood assay. Pediatr. Res., 2006, 60, 770–774.
32. Itazawa, T., Adachi, Y., Nakabayashi, M., Fuchizawa, T., Murakami, G., Miyawaki, T. Theophylline metabolism in acute asthma with MxA-indicated viral infection. Pediatr. Int., 2006, 48, 54–57.
33. Ronni, T., Melen, K., Malygin, A., Julkunen, I. Control of IFN inducible MxA gene expression in human cells. J. Immunol., 1993, 150, 1715–26.
34. Huang, N., Morlock, L., Lee, C. H., Chen, L. S., Chou, Y. J. Antibiotic prescribing for children with nasopharyngitis (common colds), upper respiratory infections, and bronchitis who have health professional parents. Pediatrics 2005, 116, 826–832.
35. Kalliolias, G. D., Ivashkiv, L. B. Overview of the biology of type I interferons. Arthritis. Res. Ther., 2010, 12, S1.
36. Toivonen L, Schuez-Havupalo L, Rulli M, Ilonen J, Pelkonen J, Melen K. Blood MxA protein as a marker for respiratory virus infections in young children. J. Clin. Virol., 2015, 62, 8–13.
37. Haller, O., Kochs, G. Human MxA protein: an interferoninduced dynamin-like GTPase with broad antiviral activity. J. Interferon Cytokine Res. 2011, 31, 79–87.
38. Engelmann, I., Dubos, F., Lobert, P. E., Houssin, C., Degas, V., Sardet, A. Diagnosis of viral infections using myxovirus resistance protein A (MxA). Pediatrics, 2015, 135, e985–93.
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2022 Issue 3
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