Differential binding efficiency between the envelope protein of Japanese encephalitis virus variants and heparan sulfate on the cell surface

Abstract

Japanese encephalitis (JE) virus infects a number of host cells, either mosquitoes or vertebrates, in nature. The viral envelope (E) protein is known to interact with molecule(s) on the cell membrane during the early stage of virus infection. In this study, two sets of virus variants including T1P1-L4/T1P1-S1 and CJN-L1/CJN-S1 derived from two strains (T1P1 and CJN) of the JE virus were used to evaluate the effects of genomic variations on virus entry. Each set of virus variant (T1P1-L4/T1P1-S1 or CJN-L1/CJN-S1) possessed a single amino acid variation in the E protein. The variation of Glu/Lys at E-306 was found between T1P1-L4 and T1P1-S1 whereas the same variation at E-138 was seen between CJN-L1 and CJN-S1. The results showed that heparan sulfate (HS) differentially expressed on the surface of different types of host cells was essential for JE virus infection as shown in an evident difference in attachment efficiency between CHO-K1 cells and its mutant with defects in GAG biosynthesis. Furthermore, differential interaction of heparin with the envelope protein of JE virus variants implies the significance of virus mutations (especially Lys for E-138 and/or E306 in this case) that are rather likely involved in determining efficiencies of viral attachment, penetration, and eventual infection.

Intrinsically Disordered Side of the Zika Virus Proteome

“…Structurally, ZIKV M protein is characterized by N-terminal soluble loop (M loop) which contain two short α-helices (residues 6–10 and 21–39) and two transmembrane α-helices (residues 40–52 and 56–71) connected by very short loop that forms the stem and the transmembrane part of this protein embedded in the lipid bilayer. (Liu et al, 2004; Sirohi et al, 2016). Curiously, although the soluble M loop is predicted to be mostly disordered and contains little regular secondary structure in the E-M complex, it is crucial for stabilization of the E-M dimer, being intercalated into the E protein structure.…”

The roles of CD81 and glycosaminoglycans in the adsorption and uptake of infectious HCV particles

“…HCV belongs to the Hepacivirus genus of the Flaviridae family [Shukla et al, 1995;Major and Feinstone, 1997]. The GAG, heparan sulfate proteoglycan (HSPG), is expressed at the surface of most mammalian cells [Rabenstein, 2002] and constitutes an important cellular-binding molecule for several members of Flaviridae family, such as dengue [Chen et al, 1997;Hilgard and Stockert, 2000;Germi et al, 2002a,b], classical swine fever [Hulst et al, 2001], yellow fever [Germi et al, 2002a,b], tick-borne encephalitis [Mandl et al, 2001] and Japanese encephalitis viruses [Su et al, 2001;Lee et al, 2004;Liu et al, 2004;Zhao et al, 2005]. Internalization of flaviviruses is thought to occur after binding to GAG residues, and other molecules are also involved in virus entry.…”

Heparan sulfate binding by natural eastern equine encephalitis viruses promotes neurovirulence

“…HS is a ubiquitous, sulfated polysaccharide glycosaminoglycan (GAG), which is expressed as a component of extracellular matrices and on cell surfaces (15,16) and is used by some viruses as an initial cell attachment receptor (17). Multiple laboratory strains of arthropod-borne alphaviruses and flaviviruses have been shown to attach to this molecule (18)(19)(20)(21)(22)(23). However, HS binding can be conferred by amino acid substitutions that arise in attachment proteins during in vitro passage (18,(24)(25)(26)(27).…”