Scolaro Luis A, Roldan Julieta S, Theaux Clara, Damonte Elsa B, Carlucci Maria J
Laboratorio de Virología, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Buenos Aires, Argentina.
Front Microbiol. 2017 Dec 22;8:2625. doi: 10.3389/fmicb.2017.02625. eCollection 2017.
Our perspective on nature has changed throughout history and at the same time has affected directly or indirectly our perception of biological processes. In that sense, the "fluxus" of information in a viral population arises a result of a much more complex process than the encoding of a protein by a gene, but as the consequence of the interaction between all the components of the genome and its products: DNA, RNA, and proteins and its modulation by the environment. Even modest "agents of life" like viruses display an intricate way to express their information. This conclusion can be withdrawn from the huge quantity of data furnished by new and potent technologies available now to analyze viral populations. Based on this premise, evolutive processes for viruses are now interpreted as a simultaneous and coordinated phenomenon that leads to global (i.e., not gradual or 'random') remodeling of the population. Our system of study involves the modulation of herpes simplex virus populations through the selective pressure exerted by carrageenans, natural compounds that interfere with virion attachment to cells. On this line, we demonstrated that the passaging of virus in the presence of carrageenans leads to the appearance of progeny virus phenotipically different from the parental seed, particularly, the emergence of syncytial (syn) variants. This event precedes the emergence of mutations in the population which can be readily detected five passages after from the moment of the appearance of syn virus. This observation can be explained taking into consideration that the onset of phenotypic changes may be triggered by "environmental-sensitive" glycoproteins. These "environmental-sensitive" glycoproteins may act by themselves or may transmit the stimulus to "adapter" proteins, particularly, proteins of the tegument, which eventually modulate the expression of genomic products in the "virocell." The modulation of the RNA network is a common strategy of the virocell to respond to environmental changes. This "fast" adaptive mechanism is followed eventually by the appearance of mutations in the viral genome. In this paper, we interpret these findings from a philosophical and scientific point of view interconnecting epigenetic action, exerted by carragenans from early RNA network-DNA interaction to late DNA mutation. The complexity of HSV virion structure is an adequate platform to envision new studies on this topic that may be complemented in a near future through the analysis of the genetic dynamics of HSV populations.
纵观历史，我们对自然的看法不断变化，同时也直接或间接地影响了我们对生物过程的认知。从这个意义上说，病毒群体中信息的“流动”源于一个比基因编码蛋白质更为复杂的过程，而是基因组及其产物（DNA、RNA和蛋白质）所有成分之间相互作用以及环境对其调节的结果。即使像病毒这样相对“简单的生命因子”也展现出一种复杂的信息表达方式。这一结论可从如今用于分析病毒群体的强大新技术所提供的海量数据中得出。基于这一前提，现在认为病毒的进化过程是一种同时发生且相互协调的现象，会导致群体的整体（即非渐进或“随机”）重塑。我们的研究系统涉及通过角叉菜胶（一种干扰病毒粒子附着细胞的天然化合物）施加的选择压力来调节单纯疱疹病毒群体。据此，我们证明了在角叉菜胶存在的情况下病毒传代导致子代病毒在表型上不同于亲代种子，特别是出现了合胞体（syn）变体。这一事件先于群体中突变的出现，在合胞体病毒出现后的五代就可轻易检测到这些突变。考虑到表型变化的起始可能由“环境敏感”糖蛋白触发，这一观察结果就能得到解释。这些“环境敏感”糖蛋白可能自身发挥作用，也可能将刺激传递给“衔接”蛋白，特别是包膜蛋白，最终调节“病毒细胞”中基因组产物的表达。RNA网络的调节是病毒细胞应对环境变化的常见策略。这种“快速”适应机制最终会伴随着病毒基因组中突变的出现。在本文中，我们从哲学和科学的角度解读这些发现，将角叉菜胶从早期RNA网络 - DNA相互作用到后期DNA突变所施加的表观遗传作用联系起来。单纯疱疹病毒粒子结构的复杂性是设想关于该主题新研究的合适平台，在不久的将来，通过分析单纯疱疹病毒群体的遗传动态，这些研究可能会得到补充。
