Glycosaminoglycan binding properties of natural venezuelan equine encephalitis virus isolates.
Equine-virulent, epidemic/epizootic strains of Venezuelan equine encephalitis (VEE) virus (VEEV) arise via mutation of progenitor enzootic strains that replicate poorly in equines. Sequencing studies have implicated positively charged amino acids on the surface of the E2 envelope glycoprotein in the acquisition of equine virulence and viremia potential, suggesting that changes in binding to cell surface glycosaminoglycans (GAGs) may mediate VEE emergence. Therefore, we evaluated the binding of natural enzootic and epizootic VEEV isolates to Chinese hamster ovary (CHO) cells expressing normal, high levels of GAGs as well as to mutant CHO cells lacking GAG expression. Binding to GAGs was not consistently associated with the epizootic phenotype, and cell culture passages resulted in increased GAG binding. The low levels of GAG binding exhibited by some low-passage, equine-virulent subtype IC VEEV strains indicate that the positive-charge E2 mutations implicated in VEE subtype IC emergence are not artifacts of laboratory passage and suggest that GAG binding does not play a major role in mediating VEE emergence. The increased GAG binding exhibited by VEEV strain CPA201 from the 1993 Mexican epizootic, when compared to that of closely related enzootic subtype IE strains, was shown to result from a Glu-to-Lys mutation at position 117 of the E2 envelope glycoprotein.
Wang
Eryu
E
Center for Tropical Diseases and Department of Pathology, University of Texas Medical Branch, Galveston 77555-0609, USA.
Brault
Aaron C
AC
Powers
Ann M
AM
Kang
Wenli
W
Weaver
Scott C
SC
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D017931:DNA Primers; D018076:DNA, Complementary; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006168:Guinea Pigs; D016296:Mutagenesis; D011485:Protein Binding; D014709:Vero Cells
D017931:DNA Primers; D018076:DNA, Complementary; D006025:Glycosaminoglycans