Details

Autor(en) / Beteiligte

• Nightingale, Katie
• Lin, Kai-Min
• Ravenhill, Benjamin J.
• Davies, Colin
• Nobre, Luis
• Fielding, Ceri A.
• Ruckova, Eva
• Fletcher-Etherington, Alice
• Soday, Lior
• Nichols, Hester
• Sugrue, Daniel
• Wang, Eddie C.Y.
• Moreno, Pablo
• Umrania, Yagnesh
• Huttlin, Edward L.
• Antrobus, Robin
• Davison, Andrew J.
• Wilkinson, Gavin W.G.
• Stanton, Richard J.
• Tomasec, Peter
• Weekes, Michael P.

Titel

High-Definition Analysis of Host Protein Stability during Human Cytomegalovirus Infection Reveals Antiviral Factors and Viral Evasion Mechanisms

Ist Teil von

• Cell host & microbe, 2018-09, Vol.24 (3), p.447-460.e11

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Human cytomegalovirus (HCMV) is an important pathogen with multiple immune evasion strategies, including virally facilitated degradation of host antiviral restriction factors. Here, we describe a multiplexed approach to discover proteins with innate immune function on the basis of active degradation by the proteasome or lysosome during early-phase HCMV infection. Using three orthogonal proteomic/transcriptomic screens to quantify protein degradation, with high confidence we identified 35 proteins enriched in antiviral restriction factors. A final screen employed a comprehensive panel of viral mutants to predict viral genes that target >250 human proteins. This approach revealed that helicase-like transcription factor (HLTF), a DNA helicase important in DNA repair, potently inhibits early viral gene expression but is rapidly degraded during infection. The functionally unknown HCMV protein UL145 facilitates HLTF degradation by recruiting the Cullin4 E3 ligase complex. Our approach and data will enable further identifications of innate pathways targeted by HCMV and other viruses. [Display omitted] •Multiplexed viral screens uncover host proteins targeted by early HCMV infection•Finding host proteins targeted for degradation by HCMV reveals immune evasion strategies•A screen of HCMV deletion mutants discovers viral factors that target >250 host proteins•HLTF is an antiviral restriction factor that is targeted for degradation by HCMV UL145 Nightingale et al. describe a multiplexed proteomic approach to discover antiviral restriction factors based on their degradation during human cytomegalovirus (HCMV) infection. Helicase-like transcription factor, an antiviral factor, is targeted by host Cullin4 E3 ligase complex for rapid degradation. HCMV UL145 hijacks Cullin4 to invoke this immune evading strategy.