[en] Type I/III interferons provide powerful and universal innate intracellular defense mechanisms against viruses. Among the antiviral effectors induced, Mx proteins of some species appear as key components of defense against influenza A viruses. It is expected that such an antiviral protein must display a platform dedicated to the recognition of said viruses. In an attempt to identify such platform in human MxA, an evolution-guided approach capitalizing on the antagonistic arms race between MxA and its viral targets and the genomic signature it left on primate genomes revealed that the surface-exposed so-called "loop L4", which protrudes from the compact structure of the MxA stalk, is a hotspot of recurrent positive selection. Since MxA is archetypic of Mx1 proteins in general, we reasoned that the L4 loop also functions as a recognition platform for influenza viruses in the Mx1 proteins of other species that had been exposed to the virus for ever. In this study, the anti-influenza activity of 5 distinct mammalian Mx1 proteins was measured by comparing the number of viral nucleoprotein-positive cells 7 h after infection in a sample of 100,000 cells expected to contain both Mx1-positive and Mx1-negative cell subpopulations. The systematic depletion (P < 0.001) of virus nucleoprotein-positive cells among equine, bubaline, porcine, and bovine Mx1-expressing cell populations compared with Mx-negative cells suggests a strong anti-influenza A activity. Looking for common anti-influenza signature elements in the sequence of these Mx proteins, we found that an aromatic residue at positions 561 or 562 in the L4 loop seems critical for the anti-influenza function and/or specificity of mammalian Mx1.
Precision for document type :
Critical notes/Edition
Disciplines :
Biotechnology
Author, co-author :
Dam Van Phai ; Université de Liège - ULiège > Doct. sc. vété. (paysage)
Desmecht, Daniel ; Université de Liège - ULiège > Département de morphologie et pathologie (DMP) > Pathologie spéciale et autopsies
Garigliany, Mutien-Marie ; Université de Liège - ULiège > Département de morphologie et pathologie (DMP) > Pathologie générale et autopsies
BUI TRAN ANH, Dao; Vietnam National University of Agriculture > Veterinary Pathology > Pathology
Van Laere, Anne-Sophie ; Université de Liège - ULiège > Département de morphologie et pathologie (DMP) > Pathologie spéciale et autopsies
Language :
English
Title :
Anti-Influenza A Virus Activities of Type I/III Interferons-Induced Mx1 GTPases from Different Mammalian Species
Ashenberg, O., Padmakumar, J., Doud, M., Bloom, J., Deep mutational scanning identifies sites in influenza nucleoprotein that affect viral inhibition by MxA (2017) PLoS Pathog, 13 (3), p. e1006288
Babiker, H., Nakatsu, Y., Yamada, K., Yoneda, A., Takada, A., Ueda, J., Hata, H., Watanabe, T., Bovine and water buffalo Mx2 genes: Polymorphism and antiviral activity (2007) Immunogenetics, 59 (1), pp. 59-67
Baise, E., Pire, G., Leroy, M., Gerardin, J., Goris, N., De Clercq, K., Kerkhofs, P., Desmecht, D., Conditional expression of type i interferon-induced bovine Mx1 GTPase in a stable transgenic vero cell line interferes with replication of vesicular stomatitis virus (2004) J Interferon Cytokine Res, 24 (9), pp. 513-521
Buragohain, L., Kumar, R., Nanda, T., Phulia, S.K., Mohanty, A.K., Kumar, S., Balhara, S., Balhara, A.K., Serum MX2 protein as candidate biomarker for early pregnancy diagnosis in buffalo (2016) Reprod Domest Anim, 51 (4), pp. 453-460
Crawshaw, T., Brown, I., Essen, S., Young, S., Significant rising antibody titres to influenza A are associated with an acute reduction in milk yield in cattle (2008) Vet J, 178 (1), pp. 98-102
Dermine, M., Desmecht, D., Vivo modulation of the innate response to pneumovirus by type-I and -III interferoninduced Bos taurus Mx1 (2012) J Interferon Cytokine Res, 32 (7), pp. 332-337
Frensing, T., Seitz, C., Heynisch, B., Patzina, C., Kochs, G., Reichl, U., Efficient influenza B virus propagation due to deficient interferon-induced antiviral activity in MDCK cells (2011) Vaccine, 29 (41), pp. 7125-7129
Gao, S., Von Der Malsburg, A., Dick, A., Faelber, K., Schroder, G.F., Haller, O., Kochs, G., Daumke, O., Structure of myxovirus resistance protein a reveals intra-and intermolecular domain interactions required for the antiviral function (2011) Immunity, 35, pp. 514-525
Garigliany, M., Cornet, A., Desmecht, D., Human/bovine chimeric MxA-like GTPases reveal a contribution of Nterminal domains to the magnitude of anti-influenza A activity (2012) J Interferon Cytokine Res, 32 (7), pp. 326-331
Haller, O., Kochs, G., Human MxA protein: An interferoninduced dynamin-like GTPase with broad antiviral activity (2011) J Interferon Cytokine Res, 31 (1), pp. 79-87
Haller, O., Staeheli, P., Schwemmle, M., Kochs, G., Mx GTPases: Dynamin-like antiviral machines of innate immunity (2015) Trends Microbiol, 23 (3), pp. 154-163
Heinz, H., Marquardt, J., Schuberth, H., Adolf, G., Leibold, W., Proteins induced by recombinant equine interferon-beta 1 within equine peripheral blood mononuclear cells and polymorphonuclear neutrophilic granulocytes (1994) Vet Immunol Immunopathol, 42 (3-4), pp. 221-235
Herfst, S., Chutinimitkul, S., Ye, J., De Wit, E., Munster, V.J., Schrauwen, E.J., Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus does not result in enhanced virulence or transmission (2010) J Virol, 84 (8), pp. 3752-3758
Hoff, F., Greb, C., Hollmann, C., Honig, E., Jacob, R., The large GTPase Mx1 is involved in apical transport in MDCK cells (2014) Traffic, 15, pp. 983-996
Isoda, N., Sakoda, Y., Kishida, N., Bai, G.R., Matsuda, K., Umemura, T., Kida, H., Pathogenicity of a highly pathogenic avian influenza virus, A/chicken/Yamaguchi/7/04 (H5N1) in different species of birds and mammals (2006) Arch Virol, 151 (7), pp. 1267-1279
Jones-Lang, K., Ernst-Larson, M., Lee, B., Goyal, S.M., Bey, R., Prevalence of influenza A virus (H1N1) antibodies in bovine sera (1998) New Microbiol, 21 (2), pp. 153-160
Landis, H., Simon-Jodicke, A., Kloti, A., Di Paolo, C., Schnorr, J.J., Schneider-Schaulies, S., Hefti, H.P., Pavlovic, J., Human MxA protein confers resistance to Semliki Forest virus and inhibits the amplification of a Semliki Forest virus-based replicon in the absence of viral structural proteins (1998) J. Virol, 72, pp. 1516-1522
Lear, T., Breen, M., Ponce De Leon, F., Coogle, L., Ferguson, E., Chambers, T., Bailey, E., Cloning and chromosomal localization of MX1 and ETS2 to chromosome 26 of the horse (Equus caballus) (1998) Chromosome Res, 6 (4), pp. 333-335
Leroy, M., Baise, E., Pire, G., Gerardin, J., Desmecht, D., Resistance of paramyxoviridae to type i interferon-induced Bos taurus Mx1 dynamin (2005) J Interferon Cytokine Res, 25 (4), pp. 192-201
Leroy, M., Pire, G., Baise, E., Desmecht, D., Expression of the interferon-alpha/beta-inducible bovine Mx1 dynamin interferes with replication of rabies virus (2006) Neurobiol Dis, 21 (3), pp. 515-521
Li, N., Zhang, L., Chen, L., Feng, W., Xu, Y., Chen, F., Liu, X., Liu, W., MxA inhibits hepatitis B virus replication by interaction with core protein HBcAg (2012) Hepatology, 56, pp. 803-811
Lopez, J., Woods, G., Epidemiological study of swine influenza virus as a component of the respiratory disease complex of feeder calves (1986) Res Commun Chem Pathol Pharmacol, 51 (3), pp. 417-420
Lopez, J.W., Woods, G.T., Response of calves to exposure with swine influenza virus (1987) Am J Vet Res, 48 (8), pp. 1264-1268
Maes, D., Deluyker, H., Verdonck, M., Castryck, F., Miry, C., Vrijens, B., De Kruif, A., Herd factors associated with the seroprevalences of four major respiratory pathogens in slaughter pigs from farrow-to-finish pig herds (2000) Vet Res, 31, pp. 313-327
Manz, B., Dornfeld, D., Gotz, V., Zell, R., Zimmermann, P., Haller, O., Kochs, G., Schwemmle, M., Pandemic influenza A viruses escape from restriction by human MxA through adaptive mutations in the nucleoprotein (2013) PLoS Pathog, 9 (3), p. e1003279
Mitchell, P., Patzina, C., Emerman, M., Haller, O., Malik, H., Kochs, G., Evolution-guided identification of antiviral specificity determinants in the broadly acting interferon-induced innate immunity factor MxA (2012) Cell Host Microbe, 12 (4), pp. 598-604
Nakajima, E., Morozumi, T., Tsukamoto, K., Watanabe, T., Plastow, G., Mitsuhashi, T., A naturally occurring variant of porcine Mx1 associated with increased susceptibility to influenza virus in vitro (2007) Biochem Genet, 45 (1-2), pp. 11-24
Nakamura, T., Asano, A., Okano, S., Ko, J.H., Kon, Y., Watanabe, T., Agui, T., Intracellular localization and antiviral property of canine Mx proteins (2005) J Interferon Cytokine Res, 25 (3), pp. 169-173
Netherton, C., Simpson, J., Haller, O., Wileman, T., Takamatsu, H., Monaghan, P., Taylor, G., Inhibition of a large doublestranded DNA virus by MxA protein (2009) J Virol, 83, pp. 2310-2320
Octaviani, C.P., Goto, H., Kawaoka, Y., Reassortment between seasonal H1N1 and pandemic (H1N1) 2009 influenza viruses is restricted by limited compatibility among polymerase subunits (2011) J Virol, 85 (16), pp. 8449-8452
Palm, M., Leroy, M., Thomas, A., Linden, A., Desmecht, D., Differential anti-influenza activity among allelic variants at the Sus scrofa Mx1 locus (2007) J Interferon Cytokine Res, 27 (2), pp. 147-155
Palm, M., Garigliany, M.M., Cornet, F., Desmecht, D., Interferon-induced Sus scrofa Mx1 blocks endocytic traffic of incoming influenza A virus particles (2010) Vet Res, 41 (3), p. 29
Seitz, C., Frensing, T., Hoper, D., Kochs, G., Reichl, U., High yields of influenza A virus in Madin-Darby canine kidney cells are promoted by an insufficient interferon-induced antiviral state (2010) J Gen Virol, 91 (100), pp. 1754-1763
Thakur, N., Singh, G., Paul, A., Bharati, J., Rajesh, G., Gm, V., Chouhan, V.S., Sarkar, M., Expression and molecular cloning of interferon stimulated genes in buffalo (Bubalus bubalis) (2017) Theriogenology, 100, pp. 50-58
Thomas, A., Palm, M., Broers, A., Zezafoun, H., Desmecht, D., Genomic structure, promoter analysis, and expression of the porcine (Sus scrofa) Mx1 gene (2006) Immunogenetics, 58 (5-6), pp. 383-389
Vahlenkamp, T., Harder, T., Influenza virus infections in mammals (2006) Berl Munch Tierarztl Wochenschr, 119 (3-4), pp. 123-131
Xie, X., Ma, K., Liu, Y., Influenza A virus infection in dogs: Epizootiology, evolution and prevention-A review (2016) Acta Vet Hung, 64 (1), pp. 125-139
Yamada, K., Nakatsu, Y., Onogi, A., Ueda, J., Watanabe, T., Specific intracellular localization and antiviral property of genetic and splicing variants in bovine Mx1 (2009) Viral Immunol, 22 (6), pp. 389-395
Zhai, S., Zhang, H., Chen, S., Zhou, X., Lin, T., Liu, R., Influenza D virus in animal species in Guangdong province Southern China (2017) Emerg Infect Dis, 23 (8), pp. 1392-1396
Zimmermann, P., Manz, B., Haller, O., Schwemmle, M., Kochs, G., The viral nucleoprotein determines Mx sensitivity of influenza A viruses (2011) J Virol, 85 (16), pp. 8133-8140