Viral Attenuation and Adaptation to Multiple Hosts

病毒减毒和对多个宿主的适应

• 批准号: 9726902
• 负责人: James Bull
• 金额: $ 14.4万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-03-01 至 2002-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9726902&HistoricalAwards=false
• 关键词: Viral; Attenuation; Adaptation; Multiple; Hosts

Bull 9726902 Many viruses infect several host species. Yet the process by which a virus adapts to multiple hosts as well as expands to new hosts is not known. Viruses that infect multiple species often consist of strains that are individually adapted to some hosts, with other strains adapted to other hosts. Introduction of a virus into a new host species may result in infections that are not propagated in that species (e.g., human infections by Ebola, hanta, and rabies virus) or may cause devastating epidemics (HIV in humans, seal plague in harbor seals, canine distemper virus in lions). Virologists have long exploited differential adaptation among alternative hosts by creating vaccines for one species either from viruses of a closely-related species or by growing viruses in cultured cells of another species to attenuate virulence. This study will develop a bacteriophage system to study adaptation to a pair of host species. Preliminary work with the phage phi X174 has revealed a one-sided adaptation: prolonged growth on one of the hosts results in changes that inhibit growth on the other host, but growth on the other host does not have the corresponding effect. The proposed work will explore this host-specific adaptation under a wide range of long term and short term conditions, monitoring fitness and genotype changes that accompany the adaptation. The study should establish a framework for the larger realm of host-specific adaptation and attenuation in viruses. More generally, the work is an experimental system of the genetic basis of adaptation that offers a level of manipulation and thoroughness of genetic and fitness assay that has not been achieved in other systems.

公牛 9726902 许多病毒感染几种宿主物种。 然而，病毒适应多个宿主以及扩展到新宿主的过程尚不清楚。 感染多个物种的病毒通常由单独适应某些宿主的菌株组成，其他菌株适应其他宿主。 将病毒引入新的宿主物种可能导致在该物种中不繁殖的感染（例如，人类感染埃博拉病毒、汉他病毒和狂犬病病毒）或可能导致毁灭性的流行病（人类感染艾滋病毒、斑海豹感染海豹鼠疫、狮子感染犬瘟热病毒）。 长期以来，病毒学家一直在利用不同宿主之间的差异适应性，为一个物种创造疫苗，或者从一个密切相关的物种的病毒中，或者通过在另一个物种的培养细胞中培养病毒来减弱毒力。 本研究将建立一个噬菌体系统来研究对一对宿主物种的适应性。 对噬菌体phi X174的初步研究揭示了一种片面的适应：在一种宿主上长时间生长会导致抑制另一种宿主生长的变化，但在另一种宿主上的生长不会产生相应的影响。 拟议的工作将探索这种宿主特异性适应在广泛的长期和短期条件下，监测健身和基因型变化，伴随着适应。 这项研究应该为病毒中宿主特异性适应和减毒的更大领域建立一个框架。 更一般地说，这项工作是一个实验系统的遗传基础的适应，提供了一个水平的操纵和彻底的遗传和健身测定，还没有实现在其他系统。