GSE111036

High definition analysis of host protein stability during human cytomegalovirus infection reveals antiviral factors and viral evasion mechanisms

Submitted by Michael Paul Weekes (University of Cambridge, United Kingdom) on Feb 23 2018

Platform: ngs – Illumina HiSeq 2500 (Homo sapiens)

Pubmed: 30122656

Summary 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 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.

9 Samples

ID	Title	Cell Type	Timepoint	Reported Virus	Virus Species
GSM3020692	HCMV_0h rep1	foreskin fibroblast cell line		HCMV	Uninfected
GSM3020693	HCMV_0h rep2	foreskin fibroblast cell line		HCMV	Uninfected
GSM3020694	HCMV_0h rep3	foreskin fibroblast cell line		HCMV	Uninfected
GSM3020695	HCMV_24h rep1	foreskin fibroblast cell line	24 hrs	HCMV	Human betaherpesvirus 5
GSM3020696	HCMV_24h rep2	foreskin fibroblast cell line	24 hrs	HCMV	Human betaherpesvirus 5
GSM3020697	HCMV_24h rep3	foreskin fibroblast cell line	24 hrs	HCMV	Human betaherpesvirus 5
GSM3020698	HCMV_72h rep1	foreskin fibroblast cell line	72 hrs	HCMV	Human betaherpesvirus 5
GSM3020699	HCMV_72h rep2	foreskin fibroblast cell line	72 hrs	HCMV	Human betaherpesvirus 5
GSM3020700	HCMV_72h rep3	foreskin fibroblast cell line	72 hrs	HCMV	Human betaherpesvirus 5