title: 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.
authors: Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors: Osvaldo
authors: O
authors: Martinez
authors: Lee
authors: L
authors: Tantral
authors: Nirupama
authors: N
authors: Mulherkar
authors: Kartik
authors: K
authors: Chandran
authors: Christopher F
authors: CF
authors: Basler
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D029043:Ebolavirus / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology / Q000821:virology; D006801:Humans; D051379:Mice; D017434:Protein Structure, Tertiary; D058425:Vaccines, Virus-Like Particle / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D006023:Glycoproteins; D058425:Vaccines, Virus-Like Particle; D014764:Viral Proteins