Krause, Melanie;
Samolej, Jerzy;
Yakimovich, Artur;
Kriston-Vizi, Janos;
Huttunen, Moona;
Lara-Reyna, Samuel;
Frickel, Eva-Maria;
(2024)
Vaccinia virus subverts xenophagy through phosphorylation and nuclear targeting of p62.
Journal of Cell Biology
, 223
(6)
, Article e202104129. 10.1083/jcb.202104129.
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Abstract
Autophagy is an essential degradation program required for cell homeostasis. Among its functions is the engulfment and destruction of cytosolic pathogens, termed xenophagy. Not surprisingly, many pathogens use various strategies to circumvent or co-opt autophagic degradation. For poxviruses, it is known that infection activates autophagy, which however is not required for successful replication. Even though these complex viruses replicate exclusively in the cytoplasm, autophagy-mediated control of poxvirus infection has not been extensively explored. Using the prototypic poxvirus, vaccinia virus (VACV), we show that overexpression of the xenophagy receptors p62, NDP52, and Tax1Bp1 restricts poxvirus infection. While NDP52 and Tax1Bp1 were degraded, p62 initially targeted cytoplasmic virions before being shunted to the nucleus. Nuclear translocation of p62 was dependent upon p62 NLS2 and correlated with VACV kinase mediated phosphorylation of p62 T269/S272. This suggests that VACV targets p62 during the early stages of infection to avoid destruction and further implies that poxviruses exhibit multi-layered control of autophagy to facilitate cytoplasmic replication.
| Type: | Article |
|---|---|
| Title: | Vaccinia virus subverts xenophagy through phosphorylation and nuclear targeting of p62 |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1083/jcb.202104129 |
| Publisher version: | http://dx.doi.org/10.1083/jcb.202104129 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Autophagy, Vaccinia virus, Phosphorylation, Humans, Cell Nucleus, HeLa Cells, Nuclear Proteins, Sequestosome-1 Protein, Virus Replication, Vaccinia, HEK293 Cells, Active Transport, Cell Nucleus |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10192153 |
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