Natural Variation in the Heparan Sulfate Binding Domain of the Eastern Equine Encephalitis Virus E2 Glycoprotein Alters Interactions with Cell Surfaces and Virulence in Mice

GARDNER, Christina L, Jo CHOI-NURVITADHI, Chengqun SUN, Avraham BAYER, Jozef HRITZ, Kate D RYMAN a William B KLIMSTRA. Natural Variation in the Heparan Sulfate Binding Domain of the Eastern Equine Encephalitis Virus E2 Glycoprotein Alters Interactions with Cell Surfaces and Virulence in Mice. JOURNAL OF VIROLOGY. WASHINGTON: AMER SOC MICROBIOLOGY, roč. 87, č. 15, s. 8582-8590. ISSN 0022-538X. doi:10.1128/JVI.00937-13. 2013.

Základní údaje

• Originální název: Natural Variation in the Heparan Sulfate Binding Domain of the Eastern Equine Encephalitis Virus E2 Glycoprotein Alters Interactions with Cell Surfaces and Virulence in Mice
• Autoři: GARDNER, Christina L, Jo CHOI-NURVITADHI, Chengqun SUN, Avraham BAYER, Jozef HRITZ, Kate D RYMAN a William B KLIMSTRA.
• Vydání: JOURNAL OF VIROLOGY, WASHINGTON, AMER SOC MICROBIOLOGY, 2013, 0022-538X.

Další údaje

• Originální jazyk: angličtina
• Typ výsledku: Článek v odborném periodiku
• Obor: 10600 1.6 Biological sciences
• Stát vydavatele: Velká Británie a Severní Irsko
• Utajení: není předmětem státního či obchodního tajemství
• Impakt faktor: Impact factor: 4.648
• Organizační jednotka: Středoevropský technologický institut
• Doi: http://dx.doi.org/10.1128/JVI.00937-13
• UT WoS: 000321590200029
• Klíčová slova anglicky: ross-river-virus; sindbis virus; flavobacterium-heparinum
• Štítky: ne MU
• Příznaky: Mezinárodní význam, Recenzováno

Anotace

Recently, we compared amino acid sequences of the E2 glycoprotein of natural North American eastern equine encephalitis virus (NA-EEEV) isolates and demonstrated that naturally circulating viruses interact with heparan sulfate (HS) and that this interaction contributes to the extreme neurovirulence of EEEV (C. L. Gardner, G. D. Ebel, K. D. Ryman, and W. B. Klimstra, Proc. Natl. Acad. Sci. U. S. A., 108:16026-16031, 2011). In the current study, we have examined the contribution to HS binding of each of three lysine residues in the E2 71-to-77 region that comprise the primary HS binding site of wild-type (WT) NA-EEEV viruses. We also report that the original sequence comparison identified five virus isolates, each with one of three amino acid differences in the E2 71-to-77 region, including mutations in residues critical for HS binding by the WT virus. The natural variant viruses, which possessed either a mutation from lysine to glutamine at E2 71, a mutation from lysine to threonine at E2 71, or a mutation from threonine to lysine at E2 72, exhibited altered interactions with heparan sulfate and cell surfaces and altered virulence in a mouse model of EEEV disease. An electrostatic map of the EEEV E1/E2 heterotrimer based upon the recent Chikungunya virus crystal structure (J. E. Voss, M. C. Vaney, S. Duquerroy, C. Vonrhein, C. Girard-Blanc, E. Crublet, A. Thompson, G. Bricogne, and F. A. Rey, Nature, 468:709-712, 2010) showed the HS binding site to be at the apical surface of E2, with variants affecting the electrochemical nature of the binding site. Together, these results suggest that natural variation in the EEEV HS binding domain may arise during EEEV sylvatic cycles and that this variation may influence receptor interaction and the severity of EEEV disease.