SR-BI Interactome Analysis Reveals a Proviral Role for UGGT1 in Hepatitis C Virus Entry

Abstract

Hepatitis C virus (HCV) entry is mediated by multiple co-receptors including scavenger receptor class B, type I (SR-BI). To elucidate the interactome of human SR-BI, we performed immunoprecipitation (IP) experiment coupled with mass spectrometry (MS) analysis. UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1), a key component of calnexin cycle involved in protein glycosylation, was identified as a SR-BI-interacting protein. Silencing UGGT1 or N-glycosylation inhibitor treatment reduced SR-BI protein level. Further study demonstrated that human SR-BI was N-glycosylated at nine asparagines. Moreover, HCV entry and infection were reduced by the absence of UGGT1. Interestingly, silencing SR-BI reduced protein stability of UGGT1 and protein quality control function mediated by UGGT1. Our finding not only identified UGGT1 as a HCV host factor, but also identified a UGGT1-mediated protein folding function for SR-BI.

Viral and host heterogeneity and their effects on the viral life cycle

“…hosts, leading to differential receptor avidity during viral infection [31][32][33][34][35][36][37][38] . The arenavirus Lassa virus preferentially enters cells that express α dystroglycan (α DG) modified with long chain matriglycans 39 .…”

“…2a). Glycosylation of human scavenger receptor class B type I (SR BI), an HCV co receptor 41,42 , is thought to be mediated by UDP glucose:glycoprotein glucosyltransferase 1 (UGGT1) 34 . Silencing of UGGT1 or inhibition of N linked glycosylation of SR BI reduces its expression, and this diminishes HCV entry 34 .…”

“…Glycosylation of human scavenger receptor class B type I (SR BI), an HCV co receptor 41,42 , is thought to be mediated by UDP glucose:glycoprotein glucosyltransferase 1 (UGGT1) 34 . Silencing of UGGT1 or inhibition of N linked glycosylation of SR BI reduces its expression, and this diminishes HCV entry 34 . SR BI is also a receptor for high density lipoprotein (HDL) and some individuals with high HDL levels carry the SR BI variant T175A 33 , which not only interferes with removal of HDL but also disrupts SR BI glycosylation and does not support SR BI mediated HCV entry 43 .…”

Self-Assembled Nanotubes Based on Chiral H8-BINOL Modified with 1,2,3-Triazole to Recognize Bi3+ Efficiently by ICT Mechanism

“…Bi 3+ is also highly sought after in the cosmetic and pharmaceutical industries, where it is commonly incorporated into eye shadows, lipsticks and hair dyes to provide the desired aesthetic properties [ 22 ]. In the pharmaceutical industry, Bi 3+ is used as an active pharmaceutical ingredient, particularly for the treatment of syphilis, peptic ulcers and hypertension [ 23 , 24 ]. It has been found that Bi 3+ significantly improves the efficacy of various drugs, such as antibiotics and anti-inflammatory drugs.…”

A quinolin-8-ol sub-millimolar inhibitor of UGGT, the ER glycoprotein folding quality control checkpoint

“…UGGT is inhibited by its product UDP (8) and by the non-hydrolysable UDP-Glucose (UDP-Glc) analogue UDP-2-deoxy-2-fluoro-D-glucose (U2F) but neither molecule is specific. Selective and potent UGGT modulators would be important reagents for cell biology for interrogating the cell biology of the secretory pathway, as well as having therapeutic potential in several areas of medical science, such as virology (9)(10)(11), rare genetic disease (12,13) and cancer (14)(15)(16). Selective and potent UGGT activity modulators also have potential applications in biotechnology and agricultural science (17)(18)(19)(20).…”