Multiomics Analysis of Endocytosis upon HBV Infection and Identification of SCAMP1 as a Novel Host Restriction Factor against HBV Replication

Abstract

Hepatitis B virus (HBV) infection remains a major global health problem and the primary cause of cirrhosis and hepatocellular carcinoma (HCC). HBV intrusion into host cells is prompted by virus–receptor interactions in clathrin-mediated endocytosis. Here, we report a comprehensive view of the cellular endocytosis-associated transcriptome, proteome and ubiquitylome upon HBV infection. In this study, we quantified 273 genes in the transcriptome and 190 endocytosis-associated proteins in the proteome by performing multi-omics analysis. We further identified 221 Lys sites in 77 endocytosis-associated ubiquitinated proteins. A weak negative correlation was observed among endocytosis-associated transcriptome, proteome and ubiquitylome. We found 33 common differentially expressed genes (DEGs), differentially expressed proteins (DEPs), and Kub-sites. Notably, we reported the HBV-induced ubiquitination change of secretory carrier membrane protein (SCAMP1) for the first time, differentially expressed across all three omics data sets. Overexpression of SCAMP1 efficiently inhibited HBV RNAs/pgRNA and secreted viral proteins, whereas knockdown of SCAMP1 significantly increased viral production. Mechanistically, the EnhI/XP, SP1, and SP2 promoters were inhibited by SCAMP1, which accounts for HBV X and S mRNA inhibition. Overall, our study unveils the previously unknown role of SCAMP1 in viral replication and HBV pathogenesis and provides cumulative and novel information for a better understanding of endocytosis in response to HBV infection.

Dissection of mRNA ac4C acetylation modifications in AC and Nr fruits: insights into the regulation of fruit ripening by ethylene

“…They were mapped to the reference genome of Solanum lycopersicum from https://solgenomics.net/ftp/tomato_genome/annotation/ITAG4.0_release/ using STAR software (version 2.5.3a) with default parameters. Reads mapped to the exon regions of each gene were counted by featureCounts (Subread-1.5.1; Bioconductor) and then RPKM was calculated (Yousaf et al 2022 ). Genes differentially expressed between groups were identified using the edgeR package (version 3.12.1) (Yousaf et al 2022 ).…”

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“…Results implied that upregulation of SCAMP1 effectively impeded HBV RNAs and proteins secretion, while SCAMP1 knockdown remarkably grew viral production. Altogether, these two multi-omics studies' ndings supply helpful knowledge to develop novel therapeutics and an exhaustive understanding of The role of HBV in HCC pathogenesis (137).…”

“…was evolved to determine the metabolic alterations in HepG2 HCC cells transfected with HBc. In other words, HBc boosts the secretion and expression of essential metabolites in HCC cells, mainly by triggering the glycolysis and amino acid metabolism pathways (137). Recently a group of researchers gave a thorough perspective of the cellular endocytosis-associated proteome, transcriptome, and ubiquitylome over HBV infection using multi-omics integration methods to shed insight on the replication and pathogenesis of HPV.…”

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“…The results of a similar study demonstrated that an upregulation of ZAP in cultured primary human hepatocytes as well as hepatocyte-derived cells was detected as a result of either IFN-α treatment or the activation of IPS-1. Knock-down of the expression of ZAP was shown to increase the HBV RNA levels and cause a partial attenuation of the antiviral effect stimulated by IPS-1 in the cell cultures used [31]. Consequently, ZAP was demonstrated as an intrinsic host antiviral factor that is active against HBV and plays a major role in the HBV replication innate control [79].…”

“…The two human zinc finger antiviral protein (hZAP) isoforms (i.e., h-ZAP S; h-ZAP L) inhibited the replication of HBV in human hepatocyte-derived cells [31].…”