Glycoprotein N of human cytomegalovirus protects the virus from neutralizing antibodies.
Glycoprotein N of human cytomegalovirus protects the virus from neutralizing antibodies.
复制标题
DOI：
10.1371/journal.ppat.1002999
复制
发表时间：
2012
期刊：
影响因子：
6.7
通讯作者：
Mach M
中科院分区：
文献类型：
--
作者：
Kropff B;Burkhardt C;Schott J;Nentwich J;Fisch T;Britt W;Mach M
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. Herpes viruses are transmitted between individuals in cell free form and successful spread benefits from mechanisms that limit the loss of infectivity by the activity of virus neutralizing antibodies. Human cytomegalovirus (HCMV) is an important pathogen and understanding how the virus can evade antiviral antibodies may be clinically relevant. HCMV particles contain a number of highly polymorphic, extensively glycosylated envelope proteins, one of which is glycoprotein N (gN). This protein is essential for replication of HCMV. We have hypothesized that the extensive glycosylation of gN may serve as a tool to evade neutralization by antiviral antibodies. Recombinant viruses were generated expressing gN proteins with reduced glycan modification. The loss of glycan modification had no detectable influence on the in vitro replication of the respective viruses. However, the recombinant viruses containing under-glycosylated forms of gN were significantly more susceptible to neutralization by a diverse array of antibody reactivities. Immunization of mice with viruses carrying fewer glycan modification induced significantly higher antibody titers against the homologous virus; however, the neutralization titers against the fully glycosylated virions, were not enhanced. Our results indicate that glycosylation of gN of HCMV represents a potentially important mechanism for evasion of antibody-mediated neutralization by a number of different antibody specificities.
登录
查看更多内容
影响因子：
3.5
作者：
CHEREPANOV, PP;WACKERNAGEL, W
通讯作者：
WACKERNAGEL, W
DOI：
10.1126/science.1185350
发表时间：
2010-04-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hansen SG;Powers CJ;Richards R;Ventura AB;Ford JC;Siess D;Axthelm MK;Nelson JA;Jarvis MA;Picker LJ;Früh K
通讯作者：
Früh K
影响因子：
3.8
作者：
Burkhardt, Christiane;Himmelein, Susanne;Mach, Michael
通讯作者：
Mach, Michael
影响因子：
19
作者：
Compton, T
通讯作者：
Compton, T
影响因子：
3.8
作者：
Davison, AJ;Dolan, A;Hayward, GS
通讯作者：
Hayward, GS