title: Glycoprotein N of human cytomegalovirus protects the virus from neutralizing antibodies.
abstract: Herpes viruses persist in the infected host and are transmitted between hosts in the presence of a fully functional humoral immune response, suggesting that they can evade neutralization by antiviral antibodies. Human cytomegalovirus (HCMV) encodes a number of polymorphic highly glycosylated virion glycoproteins (g), including the essential envelope glycoprotein, gN. We have tested the hypothesis that glycosylation of gN contributes to resistance of the virus to neutralizing antibodies. Recombinant viruses carrying deletions in serine/threonine rich sequences within the glycosylated surface domain of gN were constructed in the genetic background of HCMV strain AD169. The deletions had no influence on the formation of the gM/gN complex and in vitro replication of the respective viruses compared to the parent virus. The gN-truncated viruses were significantly more susceptible to neutralization by a gN-specific monoclonal antibody and in addition by a number of gB- and gH-specific monoclonal antibodies. Sera from individuals previously infected with HCMV also more efficiently neutralized gN-truncated viruses. Immunization of mice with viruses that expressed the truncated forms of gN resulted in significantly higher serum neutralizing antibody titers against the homologous strain that was accompanied by increased antibody titers against known neutralizing epitopes on gB and gH. Importantly, neutralization activity of sera from animals immunized with gN-truncated virus did not exhibit enhanced neutralizing activity against the parental wild type virus carrying the fully glycosylated wild type gN. Our results indicate that the extensive glycosylation of gN could represent a potentially important mechanism by which HCMV neutralization by a number of different antibody reactivities can be inhibited.
authors.affiliation: Institut für Klinische und Molekulare Virologie, Friedrich-Alexander-Universität, Erlangen-Nürnberg, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kropff
authors.forename: Christiane
authors.initials: C
authors.lastname: Burkhardt
authors.forename: Juliane
authors.initials: J
authors.lastname: Schott
authors.forename: Jens
authors.initials: J
authors.lastname: Nentwich
authors.forename: Tanja
authors.initials: T
authors.lastname: Fisch
authors.forename: William
authors.initials: W
authors.lastname: Britt
authors.forename: Michael
authors.initials: M
authors.lastname: Mach
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000821:virology; D006031:Glycosylation; D057809:HEK293 Cells; D006801:Humans; D057131:Immune Evasion; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D017384:Sequence Deletion; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014759:Viral Envelope Proteins; C417883:glycoprotein N, Human cytomegalovirus