Impact of West Nile Virus Envelope Domain III Surface Loop Residues on Antigenicity and Virulence

West Nile virus (WNV) is an encephalitic flavivirus that is maintained worldwide in a transmission cycle between birds and mosquitoes. Domain III of its envelope protein is the target of highly specific and potently neutralizing antibodies, and is thought to bind the host cell receptors. To determine the role of individual surface loop residues in the function and antigenicty of WNV EIII, a panel of mutants was generated. Changes in antibody neutralization, in vitro replication kinetics, and in vivo virulence were characterized. In general, it was found that diversity in the surface loops was well tolerated and that all surface loop residues had at least some contribution to antigenicity. Residue T332 was especially important from an antigenic standpoint. Changes at T332 resulted in escape from neutralization by monoclonal and polyclonal antibodies both in vitro and in vivo. Changes at residues G331, D333, and N368 resulted in attenuation, suggesting a possible functional patch involved in receptor binding.

Name thesis:degree_name

Experimental Pathology (Doctoral)

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Experimental Pathology

Grantor

The University of Texas Medical Branch at Galveston

Author dc:creator

• Plante, Jessica Ann

Advisor dc:contributor.advisor

• Beasley, David WC

Committee members dc:contributor.committeemember

• Barrett, Alan DT
• Lee, James C
• Pierson, Theodore C
• Tesh, Robert B

• West Nile virus
• flavivirus
• envelope domain III

Handle dc:identifier.uri

http://hdl.handle.net/2152.3/683

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/683