Attenuated West Nile virus mutant NS1130-132QQA/175A/207A exhibits virus-induced ultrastructural changes and accumulation of protein in the endoplasmic reticulum.
We have previously shown that ablation of the three N-linked glycosylation sites in the West Nile virus NS1 protein completely attenuates mouse neuroinvasiveness (≥1,000,000 PFU). Here, we compared the replication of the NS1130-132QQA/175A/207A mutant to that of the parental NY99 strain in monkey kidney Vero cells. The results suggest that the mechanism of attenuation is a lack of NS1 glycosylation, which blocks efficient replication, maturation, and NS1 secretion from the endoplasmic reticulum and results in changes to the virus-induced ultrastructure.
Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA.
Melissa C
MC
Whiteman
Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA.
Vsevolod
V
Popov
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, Texas, USA.
Michael B
MB
Sherman
Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA.
Julie
J
Wen
Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, Texas, USA Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas, USA abarrett@utmb.edu.
Alan D T
AD
Barrett
D019943:Amino Acid Substitution; D000818:Animals; D002522:Chlorocebus aethiops; D055032:Electron Microscope Tomography; D004721:Endoplasmic Reticulum / Q000737:chemistry*; D006031:Glycosylation; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D015388:Organelles / Q000648:ultrastructure*; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication; D014902:West Nile virus / Q000235:genetics / Q000502:physiology*
D050505:Mutant Proteins; D017361:Viral Nonstructural Proteins; C531936:nonstructural protein 1, West Nile virus