RT Journal Article
T1 MX2-mediated innate immunity against HIV-1 is regulated by serine phosphorylation
A1 Betancor, Gilberto
A1 Jimenez-Guardeño, Jose Manuel
A1 Lynham, Steven
A1 Antrobus, Robin
A1 Khan, Hataf
A1 Sobala, Andrew
A1 Dicks, Matthew DJ
A1 Malim, Michael H.
K1 Virología
AB 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.
PB Springer Nature
YR 2021
FD 2021
LK https://hdl.handle.net/10630/33867
UL https://hdl.handle.net/10630/33867
LA eng
NO 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
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 25 ene 2026