Proteomics

Dataset Information

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


ABSTRACT: Human cytomegalovirus (HCMV) is an important human pathogen and a paradigm of viral immune evasion, targeting intrinsic, innate and adaptive immunity. We have employed two novel, orthogonal multiplexed tandem mass tag-based proteomic screens to identify host proteins downregulated by viral factors expressed during the latest phases of viral infection. This approach revealed that the HIV-1 restriction factor Schlafen-11 (SLFN11) was degraded by the poorly characterised, late-expressed HCMV protein RL1, via recruitment of the Cullin4-RING E3 Ubiquitin Ligase (CRL4) complex. SLFN11 potently restricted HCMV infection, inhibiting the formation and spread of viral plaques. Overall, we show that a restriction factor previously thought only to inhibit RNA viruses additionally restricts HCMV. We define the mechanism of viral antagonism and also describe an important resource for revealing additional molecules of importance in antiviral innate immunity and viral immune evasion.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Cytomegalovirus Homo Sapiens (human)

TISSUE(S): Cell Culture, Fibroblast

DISEASE(S): Human Cytomegalovirus Infection

SUBMITTER: Michael Weekes  

LAB HEAD: Michael Weekes

PROVIDER: PXD026785 | Pride | 2022-02-22

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
Block_3_HpRP10A.raw Raw
Block_3_HpRP10B.raw Raw
Block_3_HpRP11A.raw Raw
Block_3_HpRP11B.raw Raw
Block_3_HpRP12A.raw Raw
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Publications

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

Nightingale Katie K   Potts Martin M   Hunter Leah M LM   Fielding Ceri A CA   Zerbe Cassie M CM   Fletcher-Etherington Alice A   Nobre Luis L   Wang Eddie C Y ECY   Strang Blair L BL   Houghton Jack W JW   Antrobus Robin R   Suarez Nicolas M NM   Nichols Jenna J   Davison Andrew J AJ   Stanton Richard J RJ   Weekes Michael P MP  

Proceedings of the National Academy of Sciences of the United States of America 20220201 6


Human cytomegalovirus (HCMV) is an important human pathogen and a paradigm of viral immune evasion, targeting intrinsic, innate, and adaptive immunity. We have employed two orthogonal multiplexed tandem mass tag-based proteomic screens to identify host proteins down-regulated by viral factors expressed during the latest phases of viral infection. This approach revealed that the HIV-1 restriction factor Schlafen-11 (SLFN11) was degraded by the poorly characterized, late-expressed HCMV protein RL1  ...[more]

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