Human cytomegalovirus protein RL1 degrades the antiviral factor SLFN11 via recruitment of the CRL4 E3 ubiquitin ligase complex | Zendy

Katie Nightingale | Zendy; Martin Potts | Zendy; Leah M. Hunter | Zendy; Ceri A. Fielding | Zendy; Cassie Zerbe | Zendy; Alice Fletcher-Etherington | Zendy; Luís Nobre | Zendy; Eddie C. Y. Wang | Zendy; Blair L. Strang | Zendy; Jack W. Houghton | Zendy; Robin Antrobus | Zendy; Nicolás M. Suárez | Zendy; Jenichols | Zendy; Andrew J. Davison | Zendy; Richard J. Stanton | Zendy; Michael P. Weekes | Zendy

Open Access

Human cytomegalovirus protein RL1 degrades the antiviral factor SLFN11 via recruitment of the CRL4 E3 ubiquitin ligase complex

Author(s) -

Katie Nightingale,

Martin Potts,

Leah M. Hunter,

Ceri A. Fielding,

Cassie Zerbe,

Alice Fletcher-Etherington,

Luís Nobre,

Eddie C. Y. Wang,

Blair L. Strang,

Jack W. Houghton,

Robin Antrobus,

Nicolás M. Suárez,

Jenichols,

Andrew J. Davison,

Richard J. Stanton,

Michael P. Weekes

Publication year - 2022

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.011

H-Index - 771

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.2108173119

Subject(s) - ubiquitin ligase , biology , innate immune system , virology , human cytomegalovirus , immune system , samhd1 , immunity , cytomegalovirus , virus , ubiquitin , microbiology and biotechnology , immunology , rna , viral disease , herpesviridae , genetics , gene , reverse transcriptase

Significance Previous proteomic analyses of host factors targeted for down-regulation by human cytomegalovirus (HCMV) have focused on early or intermediate stages of infection. Using multiplexed proteomics, we have systematically identified viral factors that target each host protein down-regulated during the latest stage of infection, after the onset of viral DNA replication. Schlafen-11 (SLFN11), an interferon-stimulated gene and restriction factor for retroviruses and certain RNA viruses, potently restricted HCMV infection. Our discovery that the late-expressed HCMV protein RL1 targets SLFN11 for proteasomal degradation provides evidence for a viral antagonist of this critical cellular protein. We therefore redefine SLFN11 as an important factor that targets DNA viruses as well as RNA viruses, offering therapeutic potential via molecules that inhibit RL1-mediated SLFN11 degradation.

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