Glycoprotein N subtypes of human cytomegalovirus induce a strain-specific antibody response during natural infection
Glycoprotein N subtypes of human cytomegalovirus induce a strain-specific antibody response during natural infection
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DOI：
10.1099/vir.0.010967-0
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发表时间：
2009-08-01
影响因子：
3.8
通讯作者：
Mach, Michael
中科院分区：
文献类型：
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作者：
Burkhardt, Christiane;Himmelein, Susanne;Mach, Michael
人巨细胞病毒(HCMV)编码多种高度多态的包膜糖蛋白，但这种多态之间的生物学相关性尚不清楚。糖蛋白N(Gn)是这种多态蛋白家族的成员之一。目前已鉴定出四种主要的gn基因(gn1-4)。我们已经验证了这样的假设，即gn多态代表了一种逃避中和抗病毒抗体反应的机制。以人巨细胞病毒AD169株的遗传背景为基础，构建了4株仅表达gn基因差异的重组病毒。Gn基因的互换对病毒复制、gn表达和gn-GM复合体的形成影响较小。随机选择人血清进行中和抗重组病毒活性分析。在这些病毒中，70%的病毒之间的中和滴度没有差异，而30%的病毒具有毒株特异性的中和能力。50%中和滴度的差异达到>；8倍。表达gN4基因的病毒中和效果明显好于表达其他gn基因的病毒。株系特异性或缺乏不能归因于抗gn抗体的存在或不存在，因为所有血清都含有与gn反应的抗体(通过酶联免疫吸附试验确定)。因此，gn基因的多态可能有助于逃避有效的中和抗体反应，并促进先前血清阳性个体的再次感染。
Human cytomegalovirus (HCMV) encodes several highly polymorphic envelope glycoproteins; however, the biological relevance of this polymorphism is unclear. Glycoprotein N (gN) is one member of this polymorphic protein family. Four major gN genotypes (gN1-4) have been identified. We have tested the hypothesis that the gN polymorphism represents a mechanism to evade a neutralizing antiviral antibody response. Four recombinant viruses that differed only in the expression of the gN genotype were constructed on the genetic background of HCMV strain AD169. Exchange of gN genotypes had a minor detectable influence on virus replication, gN expression and gN-gM complex formation. Randomly selected human sera were analysed for neutralizing activity against the recombinant viruses. Of these, 70% showed no difference in neutralizing titre between the viruses, whereas 30% showed strain-specific neutralization. Differences in 50% neutralization titre reached >8-fold. Viruses expressing the gN4 genotype were neutralized significantly better than those expressing the other gN genotypes. Strain specificity, or lack thereof, could not be attributed to the presence or absence of anti-gN antibodies, as all sera contained antibodies reacting with gN (as determined by ELISA). Thus, polymorphism of gN could contribute to evasion of an efficient neutralizing-antibody response and facilitate reinfection in previously seropositive individuals.