2026-06-02T06:08:43Zhttps://riuma.uma.es/rest/oai/request

oai:riuma.uma.es:10630/338672026-02-03T10:49:49Zcom_10630_2254col_10630_37953

MX2-mediated innate immunity against HIV-1 is regulated by serine phosphorylation Betancor, Gilberto Jimenez-Guardeño, Jose Manuel Lynham, Steven Antrobus, Robin Khan, Hataf Sobala, Andrew Dicks, Matthew DJ Malim, Michael H. Virología The antiviral cytokine interferon activates expression of interferon-stimulated genes to establish an antiviral state. Myxovirus resistance 2 (MX2, also known as MxB) is an interferon-stimulated gene that inhibits the nuclear import of HIV-1 and interacts with the viral capsid and cellular nuclear transport machinery. Here, we identified the myosin light chain phosphatase (MLCP) subunits myosin phosphatase target subunit 1 (MYPT1) and protein phosphatase 1 catalytic subunit-β (PPP1CB) as positively-acting regulators of MX2, interacting with its amino-terminal domain. We demonstrated that serine phosphorylation of the N-terminal domain at positions 14, 17 and 18 suppresses MX2 antiviral function, prevents interactions with the HIV-1 capsid and nuclear transport factors, and is reversed by MLCP. Notably, serine phosphorylation of the N-terminal domain also impedes MX2-mediated inhibition of nuclear import of cellular karyophilic cargo. We also found that interferon treatment reduces levels of phosphorylation at these serine residues and outline a homeostatic regulatory mechanism in which repression of MX2 by phosphorylation, together with MLCP-mediated dephosphorylation, balances the deleterious effects of MX2 on normal cell function with innate immunity against HIV-1. 2024-09-28T17:39:22Z 2024-09-28T17:39:22Z 2021 journal article Betancor, G., Jimenez-Guardeño, J.M., Lynham, S. et al. MX2-mediated innate immunity against HIV-1 is regulated by serine phosphorylation. Nat Microbiol 6, 1031–1042 (2021). https://doi.org/10.1038/s41564-021-00937-5 https://hdl.handle.net/10630/33867 10.1038/s41564-021-00937-5 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Springer Nature