Experimental Population Biology and Genetics of Virus Virulence

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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.