Superinfection as a driver of genomic diversification in antigenically variant pathogens
Superinfection as a driver of genomic diversification in antigenically variant pathogens
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DOI：
10.1073/pnas.0710333105
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发表时间：
2008-02-12
影响因子：
11.1
通讯作者：
Palmer, Guy H.
中科院分区：
文献类型：
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作者：
Futse, James E.;Brayton, Kelly A.;Palmer, Guy H.
一种新的病原体菌株只有在能够逃避针对原始菌株产生的免疫时才能渗透到免疫宿主群体中。这种模式在流感病毒中得到了最好的理解，其中遗传漂变产生了抗原性不同的毒株，尽管存在对先前毒株的免疫力，但这些毒株仍可以在宿主群体中传播。这种新菌株的选择模型是否适用于导致地方性持续感染的复杂病原体，如无形体病，回归热和昏睡病，仍然没有得到验证。这些复杂的病原体通过使用染色体编码的变体组进行快速的宿主内抗原变异。因此，针对大量变体产生免疫力，从而显著改变新菌株逃避现有免疫力并建立共存感染所需的遗传变化范围，称为菌株重复感染。在这里，我们表明，在一个高度抗原性变异病原体菌株之间的等位基因编码抗原变异的多样性是等于菌株内的多样性，反映了等价的选择变异，以克服免疫力在宿主种群水平内的一个单独的主机。菌株之间的这种多样性导致非重叠变体的表达，这使得新菌株能够逃避免疫并建立重复感染。此外，我们证明了一个独特的等位基因允许菌株重复感染。这些结果表明，有很强的选择压力，以增加变异库的多样性超出所需的持久性在一个单独的主机，并提供了一个解释，在主机人口水平上的竞争，为大的基因组承诺变异基因家族在持久性病原体。
A new pathogen strain can penetrate an immune host population only if it can escape immunity generated against the original strain. This model is best understood with influenza viruses, in which genetic drift creates antigenically distinct strains that can spread through host populations despite the presence of immunity against previous strains. Whether this selection model for new strains applies to complex pathogens responsible for endemic persistent infections, such as anaplasmosis, relapsing fever, and sleeping sickness, remains untested. These complex pathogens undergo rapid within-host antigenic variation by using sets of chromosomally encoded variants. Consequently, immunity is developed against a large repertoire of variants, dramatically changing the scope of genetic change needed for a new strain to evade existing immunity and establish coexisting infection, termed strain superinfection. Here, we show that the diversity in the alleles encoding antigenic variants between strains of a highly antigenically variant pathogen was equal to the diversity within strains, reflecting equivalent selection for variants to overcome immunity at the host population level as within an individual host. This diversity among strains resulted in expression of nonoverlapping variants that allowed a new strain to evade immunity and establish superinfection. Furthermore, we demonstrated that a single distinct allele allows strain superinfection. These results indicate that there is strong selective pressure to increase the diversity of the variant repertoire beyond what is needed for persistence within an individual host and provide an explanation, competition at the host population level, for the large genomic commitment to variant gene families in persistent pathogens.