Virus Adaptation by Manipulation of Host's Gene Expression

Viruses adapt to their hosts by evading defense mechanisms and taking over cellular metabolism for their own benefit. Alterations in cell metabolism as well as side-effects of antiviral responses contribute to symptoms development and virulence. Sometimes, a virus may spill over from its usual host species into a novel one, where usually will fail to successfully infect and further transmit to new host. However, in some cases, the virus transmits and persists after fixing beneficial mutations that allow for a better exploitation of the new host. This situation would represent a case for a new emerging virus. Here we report results from an evolution experiment in which a plant virus was allowed to infect and evolve on a naïve host. After 17 serial passages, the viral genome has accumulated only five changes, three of which were non-synonymous. An amino acid substitution in the viral VPg protein was responsible for the appearance of symptoms, whereas one substitution in the viral P3 protein the epistatically contributed to exacerbate severity. DNA microarray analyses show that the evolved and ancestral viruses affect the global patterns of host gene expression in radically different ways. A major difference is that genes involved in stress and pathogen response are not activated upon infection with the evolved virus, suggesting that selection has favored viral strategies to escape from host defenses.

病毒通过逃避宿主防御机制、接管细胞代谢以服务自身增殖需求，实现对宿主的适应。宿主细胞代谢的改变，以及抗病毒应答所带来的副作用，均会促进症状发生并增强病毒毒力。有时，病毒会从其自然宿主物种跨宿主溢出至新宿主，通常无法成功感染该新宿主并实现进一步传播。但在部分情形下，病毒可通过获得并固定有益突变，实现对新宿主的更高效利用，进而完成传播并持续存活，此种情形即代表新发病毒（emerging virus）的诞生案例。本研究报道了一项演化实验的结果：实验中一株植物病毒可在未接触过该病毒的宿主（naïve host）上完成感染与演化。经过17次连续传代后，病毒基因组仅积累了5处突变，其中3个为非同义突变（non-synonymous）。病毒VPg蛋白上的一处氨基酸替换是症状产生的关键诱因，而病毒P3蛋白上的一处替换则通过上位性作用加剧了症状严重程度。DNA微阵列分析（DNA microarray analyses）显示，演化后的病毒与原始病毒对宿主基因表达全局模式的影响截然不同。其中一项核心差异为：感染演化后的病毒时，宿主的应激与病原体应答相关基因并未被激活，这表明自然选择已倾向于让病毒演化出逃避宿主防御的策略。