Viral Attenuation and Adaptation to Multiple Hosts

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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.