Antigenic diversification is correlated with increased thermostability in a mammalian virus.
Antigenic diversification is correlated with increased thermostability in a mammalian virus.
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DOI：
10.1016/j.virol.2016.06.009
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发表时间：
2016-09
期刊：
影响因子：
3.7
通讯作者：
Novella, Isabel S.
中科院分区：
文献类型：
--
作者：
Presloid, John B.;Mohammad, Tasneem F.;Lauring, Adam S.;Novella, Isabel S.
可塑性一致性理论认为，最终，面对生物分子不稳定，维持功能的压力产生了稳健性。随着温度的升高，不稳定性也在增加。因此，遗传稳健性，定义为尽管突变的表型稳定性，应该与热挑战期间的存活相关。我们用水疱性口炎病毒（VSV）验证了这一假设。在感染期间，通过37°C预孵育和40°C孵育，我们获得了两组具有较高热稳定性的进化菌株。这些VSV种群在没有热选择的情况下变得更耐热，也更适合，表明缺乏权衡。12个进化群体中有11个在核衣壳(N)开放阅读框中有固定的非同义替换。当前者在42°C下测量时，观察到热稳定性和突变鲁棒性之间存在部分相关性，而在37°C下则没有。这些结果与我们早期的工作一致，并表明鲁棒性和热稳定性之间的关系是复杂的。令人惊讶的是，许多耐热菌株对单克隆抗体和多克隆血清（包括来自自然宿主的血清）也表现出增强的抗性。这些数据表明，进化的热稳定性可能导致抗原多样化和在发热宿主中逃避免疫监视的能力增强，并可能提高稳健性。这些关系不仅在病毒发病机制方面具有重要意义，而且对疫苗载体和溶瘤剂的开发也具有重要意义。
The theory of plastogenetic congruence posits that ultimately, the pressure to maintain function in the face of biomolecular destabilization produces robustness. As temperature goes up so does destabilization. Thus, genetic robustness, defined as phenotypic constancy despite mutation, should correlate with survival during thermal challenge. We tested this hypothesis using vesicular stomatitis virus (VSV). We produced two sets of evolved strains after selection for higher thermostability by either preincubation at 37°C or by incubation at 40°C during infection. These VSV populations became more thermostable and also more fit in the absence of thermal selection, demonstrating an absence of tradeoffs. Eleven out of 12 evolved populations had a fixed, nonsynonymous substitution in the nucleocapsid (N) open reading frame. There was a partial correlation between thermostability and mutational robustness that was observed when the former was measured at 42°C, but not at 37°C. These results are consistent with our earlier work and suggest that the relationship between robustness and thermostability is complex. Surprisingly, many of the thermostable strains also showed increased resistance to monoclonal antibody and polyclonal sera, including sera from natural hosts. These data suggest that evolved thermostability may lead to antigenic diversification and an increased ability to escape immune surveillance in febrile hosts, and potentially to an improved robustness. These relationships have important implications not only in terms of viral pathogenesis, but also for the development of vaccine vectors and oncolytic agents.
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