Structures and Functions of the Envelope Glycoprotein in Flavivirus Infections

Abstract

Flaviviruses are enveloped, single-stranded RNA viruses that widely infect many animal species. The envelope protein, a structural protein of flavivirus, plays an important role in host cell viral infections. It is composed of three separate structural envelope domains I, II, and III (EDI, EDII, and EDIII). EDI is a structurally central domain of the envelope protein which stabilizes the overall orientation of the protein, and the glycosylation sites in EDI are related to virus production, pH sensitivity, and neuroinvasiveness. EDII plays an important role in membrane fusion because of the immunodominance of the fusion loop epitope and the envelope dimer epitope. Additionally, EDIII is the major target of neutralization antibodies. The envelope protein is an important target for research to develop vaccine candidates and antiviral therapeutics. This review summarizes the structures and functions of ED I/II/III, and provides practical applications for the three domains, with the ultimate goal of implementing strategies to utilize the envelope protein against flavivirus infections, thus achieving better diagnostics and developing potential flavivirus therapeutics and vaccines.

Structure-Based Design of Antivirals against Envelope Glycoprotein of Dengue Virus

“…The C protein is important for encapsidation that protects the DENV genome [10]. The prM maintains the spatial structure of the E protein [11]. The E protein has been implicated in the membrane fusion between host cells and DENV particles [11].…”

Codelivery of improved immune complex and virus-like particle vaccines containing Zika virus envelope domain III synergistically enhances immunogenicity

“…The main antigenic determinant of the virus is the envelope glycoprotein (E), since it is displayed on the surface of the mature virus particle and can be targeted by a number of neutralizing antibodies [9,10]. Neutralizing antibodies generated by approved vaccines for yellow fever virus, Japanese encephalitis virus, and tick-borne encephalitis virus, which are closely related to ZIKV, appear to have a correlation with viral protection [11,12].…”

Computational Prediction of Multi-Epitopes Vaccine from Envelope E Protein against Louping Ill Virus via Reverse Vaccinology

“…The genome contains only one open reading frame (ORF) flanked by 5' and 3'untranslated regions (UTRs) that encodes a polyprotein. The translated polyprotein is directed into host endoplasmic reticulum (ER) membrane by signal sequences and cleaved by host protease into three structural proteins, a nucleocapsid protein (C protein), a precursor membrane glycoprotein (prM protein) and a glycosylated envelope protein (E protein), as well as seven non-structural (NS) proteins [15][16][17][18][19]. The C protein is responsible for encapsulation of the virus to protect the genetic material.…”