2026-05-28T22:19:36Zhttps://riuma.uma.es/rest/oai/request

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

00925njm 22002777a 4500 dc Betancor, Gilberto author Jimenez-Guardeño, Jose Manuel author Lynham, Steven author Antrobus, Robin author Khan, Hataf author Sobala, Andrew author Dicks, Matthew DJ author Malim, Michael H. author 2021 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. 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 Virología MX2-mediated innate immunity against HIV-1 is regulated by serine phosphorylation