Related Experiment Videos
Sialylation of the host receptor may modulate entry of demyelinating persistent Theiler's virus
1Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Abstract:
Theiler's murine encephalomyelitis virus (TMEV) is a picornavirus of the Cardiovirus genus. Certain strains of TMEV may cause a chronic demyelinating disease, which is very similar to multiple sclerosis in humans, associated with a persistent viral infection in the mouse central nervous system (CNS). Other strains of TMEV only cause an acute infection without persistence in the CNS. It has been shown that sialic acid is a receptor moiety only for the persistent TMEV strains and not for the nonpersistent strains. We report the effect of sialylation on cell surface on entry and the complex structure of DA virus, a persistent TMEV, and the receptor moiety mimic, sialyllactose, refined to a resolution of 3.0 A. The ligand binds to a pocket on the viral surface, composed mainly of the amino acid residues from capsid protein VP2 puff B, in the vicinity of the VP1 loop and VP3 C terminus. The interaction of the receptor moiety with the persistent DA strain provides new understanding for the demyelinating persistent infection in the mouse CNS by TMEV.
Insights
Persistent Theiler's murine encephalomyelitis virus (TMEV) strains use sialic acid to infect the central nervous system, causing demyelination similar to multiple sclerosis. Structural analysis reveals how the virus binds its receptor.
Area of Science:
- Virology
- Neuroscience
- Structural Biology
Background:
- Theiler's murine encephalomyelitis virus (TMEV) causes central nervous system (CNS) infections in mice.
- Certain TMEV strains induce chronic demyelinating disease, mimicking human multiple sclerosis.
- Sialic acid acts as a receptor for persistent TMEV strains but not for acute ones.
Purpose of the Study:
- To investigate the role of sialylation in cell surface entry of persistent TMEV.
- To determine the complex structure of the persistent DA virus strain and its receptor mimic, sialyllactose.
- To elucidate the molecular interactions between the TMEV receptor and the virus.
Main Methods:
- X-ray crystallography was used to refine the structure of the DA virus and sialyllactose to 3.0 A resolution.
- Analysis of the binding site and amino acid residues involved in receptor interaction.
Main Results:
- The crystal structure revealed the binding pocket for sialyllactose on the viral surface.
- The binding pocket is primarily formed by amino acid residues from capsid protein VP2 puff B, near the VP1 loop and VP3 C terminus.
- This interaction explains the specific binding of sialic acid to persistent TMEV strains.
Conclusions:
- The study provides a detailed structural understanding of how persistent TMEV strains bind to sialic acid.
- This interaction is crucial for the demyelinating persistent infection observed in the mouse CNS.
- Findings offer insights into the mechanisms underlying TMEV-induced neurological disease.