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Impact of Ebola mucin-like domain on antiglycoprotein antibody responses induced by Ebola virus-like particles.

Abstract
Ebola virus (EBOV) glycoprotein (GP), responsible for mediating host-cell attachment and membrane fusion, contains a heavily glycosylated mucin-like domain hypothesized to shield GP from neutralizing antibodies. To test whether the mucin-like domain inhibits the production and function of anti-GP antibodies, we vaccinated mice with Ebola virus-like particles (VLPs) that express vesicular stomatitis virus G, wild-type EBOV GP (EBGP), EBOV GP without its mucin-like domain (ΔMucGP), or EBOV GP with a Crimean-Congo hemorrhagic fever virus mucin-like domain substituted for the EBOV mucin-like domain (CMsubGP). EBGP-VLP immunized mice elicited significantly higher serum antibody titers toward EBGP or its mutants, as detected by western blot analysis, than did VLP-ΔMucGP. However, EBGP-, ΔMucGP- and CMsubGP-VLP immunized mouse sera contained antibodies that bound to cell surface-expressed GP at similar levels. Furthermore, low but similar neutralizing antibody titers, measured against a vesicular stomatitis virus (VSV) expressing EBGP or ΔMucGP, were present in EBGP, ΔMucGP, and CMsubGP sera, although a slightly higher neutralizing titer (2- to 2.5-fold) was detected in ΔMucGP sera. We conclude that the EBOV GP mucin-like domain can increase relative anti-GP titers, however these titers appear to be directed, at least partly, to denatured GP. Furthermore, removing the mucin-like domain from immunizing VLPs has modest impact on neutralizing antibody titers in serum.
AuthorsOsvaldo Martinez, Lee Tantral, Nirupama Mulherkar, Kartik Chandran, Christopher F Basler
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 204 Suppl 3 Pg. S825-32 (Nov 2011) ISSN: 1537-6613 [Electronic] United States
PMID21987758 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antibodies, Viral
  • Glycoproteins
  • Vaccines, Virus-Like Particle
  • Viral Proteins
Topics
  • Animals
  • Antibodies, Viral (biosynthesis)
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Disease Models, Animal
  • Ebolavirus (immunology)
  • Glycoproteins (immunology)
  • Hemorrhagic Fever, Ebola (immunology, virology)
  • Humans
  • Mice
  • Protein Structure, Tertiary
  • Vaccines, Virus-Like Particle (immunology)
  • Viral Proteins (immunology)

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