Patrick Moore described how the discovery of new pathogens will require the talents of multiple disciplines, including epidemiology, clinical medicine, molecular biology, and pathology. Moore used the example of the identification of the virus that causes Kaposi’s sarcoma, which often strikes gay men, to discuss general issues in causality and to illustrate the limits of current approaches for determining causality for a newly discovered agent and disease. The causative agent, named Kaposi’s sarcoma-associated herpesvirus (KSHV), was identified using a genetic technique called representational difference analysis. Once the virus was identified, in 1994, events moved rather quickly—a fact that speaks to the importance of new pathogen discovery. The virus’s genome has been sequenced, serologic tests have been developed, and studies have been initiated to understand its epidemiology and to test possible treatments. Moreover, the virus has since been found to cause at least two other types of disease. Based on this experience, Moore pointed to the need for researchers to move beyond Koch’s postulates or other traditional guidelines in their efforts to determine disease causality for suspect microbes. Researchers are attempting to do this by applying various new techniques emerging from molecular biology and biotechnology. It seems clear as well that epidemiologists developing new criteria for causality will have to incorporate new pathogenic mechanisms that are not accounted for in current disease models.

Mikhail Pletnikov discussed the importance of expanding research to better understand the interplay of genetic and environmental factors in the causation of a number of important developmental behavioral disorders. Among methodological problems of studying the gene-environment interplay is the difficulty in firmly defining environmental factors and making them quantifiable. In this context, virus infections provide a promising research avenue, because of their etiologic connection to several neurodevelopmental disorders, including autism and schizophrenia, and because of the reliability of quantification of viral effects on brain and behavior. In particular, Pletnikov described work using an animal model to study gene-environmental interactions that occur during neonatal infection with Borna disease virus (BDV). Neonatal BDV infection in rats has been shown to produce distinct neuroanatomical, neurochemical, and behavioral abnormalities that resemble pathological and clinical features of some human developmental disorders. The significance of studying neonatal exposure derives from the fact that the effects of many genetic and environmental risk factors are evident either prior to or around the time of birth, and the interaction between them often is apparent well before the onset or diagnosis of the chronic disease condition. Thus, studying the effects of neonatal BDV infection across the entire postnatal period in genetically different strains of rats will aid in understanding the course and time-dependent character of the interaction of genetic background features and the virus infection. In this way, the model system may allow study of some tremendously complex mechanisms relevant to developmental disorders.

David Persing provided an overview of recent research in the area of infec-



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