Alternative titles; symbols
HGNC Approved Gene Symbol: MX2
Cytogenetic location: 21q22.3 Genomic coordinates (GRCh38): 21:41,362,027-41,409,393 (from NCBI)
Huber et al. (1988) pointed out that the 2 Mx mRNAs that they isolated (MX1, 147150, and MX2) are distinct.
Melen et al. (1996) produced antibodies to cloned human MX2 (which they referred to as MxB) and examined its subcellular localization. They showed that it is found in both the cytoplasm and the nucleus, where it is localized in a granular pattern in the heterochromatin region beneath the nuclear envelope. Melen et al. (1996) used deletion analysis to define the nuclear localization signal (NLS) in the protein sequence of MxB. GTPase assays showed that MxB is a functional GTPase with activity comparable to that of MxA (147150). Analysis of peripheral blood mononuclear cells suggested to Melen et al. (1996) that MxB protein expression is strictly regulated by interferon-alpha (IFNA; 147660).
Goujon et al. (2013) used both ectopic expression and gene silencing experiments to define the human MX2 protein as a potent inhibitor of HIV-1 infection and as a key effector of IFNA-mediated resistance to HIV-1 infection. MX2 suppressed infection by all HIV-1 strains tested, had equivalent or reduced effects on divergent simian immunodeficiency viruses, and did not inhibit other retroviruses such as murine leukemia virus. The capsid region of the viral Gag protein dictates susceptibility to MX2, and the block to infection occurs at a late postentry step, with both the nuclear accumulation and chromosomal integration of nascent viral cDNA suppressed. Finally, human MX1 (147150), a closely related protein that is a broadly acting inhibitor of RNA and DNA viruses, including the orthomyxovirus influenza A virus, does not affect HIV-1, whereas MX2 is ineffective against influenza virus. Goujon et al. (2013) concluded that MX2 is a cell-autonomous, anti-HIV-1 resistance factor whose purposeful mobilization may represent a therapeutic approach for the treatment of HIV/AIDS.
By comparing gene expression profiles in cell lines that differed in their ability to support the inhibitory action of IFNA at early steps of the HIV-1 replication cycle, Kane et al. (2013) identified MX2 as an interferon-induced inhibitor of HIV-1 infection. Expression of MX2 reduced permissiveness to a variety of lentiviruses, whereas depletion of MX2 using RNA interference reduced the anti-HIV-1 potency of IFNA. HIV-1 reverse transcription proceeded normally in MX2-expressing cells, but 2-long terminal repeat circular forms of HIV-1 DNA were less abundant, suggesting that MX2 inhibits HIV-1 nuclear import, or destabilizes nuclear HIV-1 DNA. Consistent with this notion, mutations in the HIV-1 capsid protein that were known or suspected to alter the nuclear import pathways used by HIV-1 conferred resistance to MX2, whereas preventing cell division increased MX2 potency. Kane et al. (2013) concluded that these findings indicated that MX2 is an effector of the anti-HIV-1 activity of type I IFN, and suggested that MX2 inhibits HIV-1 infection by inhibiting capsid-dependent nuclear import of subviral complexes.
By Southern blot analysis of mouse-human cell hybrid DNA, Huber et al. (1988) determined that the MX1 and MX2 genes are located on chromosome 21. The mouse Mx gene is located on the distal part of chromosome 16 in the region of genetic homology to human chromosome 21.
Goujon, C., Moncorge, O., Bauby, H., Doyle, T., Ward, C. C., Schaller, T., Hue, S., Barclay, W. S., Schulz, R., Malim, M. H. Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection. Nature 502: 559-562, 2013. [PubMed: 24048477] [Full Text: https://doi.org/10.1038/nature12542]
Huber, P., Aebi, M., Grob, R., Pravtcheva, D., Ruddle, F., Haller, O. Chromosomal localization of two human Mx genes. (Abstract) Experientia 44: A84 only, 1988.
Kane, M., Yadav, S. S., Bitzegeio, J., Kutluay, S. B., Zang, T., Wilson, S. J., Schoggins, J. W., Rice, C. M., Yamashita, M., Hatziioannou, T., Bieniasz, P. D. MX2 is an interferon-induced inhibitor of HIV-1 infection. Nature 502: 563-566, 2013. [PubMed: 24121441] [Full Text: https://doi.org/10.1038/nature12653]
Melen, K., Keskinen, P., Ronni, T., Sareneva, T., Lounatmaa, K., Julkunen, I. Human MxB protein, an interferon-alpha-inducible GTPase, contains a nuclear targeting signal and is localized in the hemochromatin region beneath the nuclear envelope. J. Biol. Chem. 271: 23478-23486, 1996. [PubMed: 8798556] [Full Text: https://doi.org/10.1074/jbc.271.38.23478]