Experimental Population Biology and Genetics of Virus Virulence

公牛 9407941 恶性传染病是人类生存中最令人恐惧的生物现象之一。 从历史上的瘟疫、结核病、疟疾和肺炎到最近的出血热、艾滋病和耐药结核病的紧急情况，已知其中一些疾病感染后的死亡率超过50%。 然而，并不是所有的传染性微生物都有足够的致命性，生物学面临的一个挑战是解开致病的原因。 分子生物学在解决某些疾病的这个问题上取得了重要进展，但是关于毒力的种群生物学--为什么一种微生物的毒力形式在种群中比无毒力形式占优势--缺乏坚实的经验基础。这里提出的工作将开发这个基础使用细菌病毒作为细菌宿主的寄生物。 将进行实验以研究寄生虫感染的种群动态如何影响毒性或无毒形式的演变。 病毒DNA序列的分析将表明这些变化的遗传基础。 总之，这项研究将作为一个模型，结合分子和人口生物学方法研究疾病的毒力。

Bull 9407941 Virulent infectious diseases have been some of the most fear-provoking biological phenomena of human existence. From the historical scourges of the plague, TB, malaria, and pneumonia to the recent emergencies of hemorrhagic fever, AIDS, and the drug resistant TB, mortality rates after infection have been known to exceed 50% for some of these diseases. Yet not all infectious microbes are virulent enough to kill, and one challenge for biology is to unravel the causes of virulence. Molecular biology is making important inroads on this problem for some diseases, but the population biology of virulence -- why the virulent forms of a microbe prevail over avirulent ones in the population -- lacks a solid empirical foundation. The work proposed here will develop this foundation using bacterial virus as a parasite of a bacterial host. Experiments will be conducted to study how the population dynamics of a parasite infection influences whether a virulent or an avirulent form evolves. Assays of the viral DNA sequence will indicate the genetic bases of these changes. Overall, this study will serve as a model for uniting molecular and population biological approaches in studying disease virulence.