Journal Article

UGGT1 enhances enterovirus 71 pathogenicity by promoting viral RNA synthesis and viral replication

Huang, Peng-Nien, Wang, Jen-Ren, Arnold, Jamie J., Cameron, Craig E., Shih, Shin-Ru, Jheng, Jia-Rong

2017

Overview

Positive-strand RNA virus infections can induce the stress-related unfolded protein response (UPR) in host cells. This study found that enterovirus A71 (EVA71) utilizes host UDP-glucose glycoprotein glucosyltransferase 1 (UGGT1), a key endoplasmic reticulum protein (ER) involved in UPR, to enhance viral replication and virulence. EVA71 forms replication complexes (RCs) on cellular membranes that contain a mix of host and viral proteins to facilitate viral replication, but the components and processes involved in the assembly and function of RCs are not fully understood. Using EVA71 as a model, this study found that host UGGT1 and viral 3D polymerase co-precipitate along with other factors on membranous replication complexes to enhance viral replication. Increased UGGT1 levels elevated viral growth rates, while viral pathogenicity was observed to be lower in heterozygous knockout mice (Uggt1 +/- mice). These findings provide important insight on the role of UPR and host UGGT1 in regulating RNA virus replication and pathogenicity.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Amino Acid Sequence / Animals / Biochemistry / Biology and life sciences / Biotechnology / Cell Line, Tumor / Cell Proliferation / Cell Survival / Defense mechanisms / Dengue fever / Endoplasmic reticulum / Endoplasmic Reticulum - enzymology / Enterovirus A, Human - genetics / Enterovirus A, Human - pathogenicity / Enterovirus A, Human - physiology / Enteroviruses / Epidemics / Glucose / Glucosyltransferase / Glucosyltransferases - genetics / Glucosyltransferases - metabolism / Glycoproteins / Growth rate / Hepatitis / Host-Pathogen Interactions / Infections / Laboratories / Medicine / Medicine and Health Sciences / Membranes / Mice / Mice, Knockout / Molecular biology / Pathogenicity / Pathogens / Protein folding / Proteins / Replication / Research and Analysis Methods / Ribonucleic acid / RNA / RNA polymerase / RNA viruses / RNA, Viral - analysis / RNA, Viral - genetics / Science / Transcription / Unfolded Protein Response / Viral infections / Viral Proteins - genetics / Viral Proteins - metabolism / Virology / Virulence / Virulence - genetics / Virus Replication - genetics / Viruses / West Nile virus