Human retroviral induced diseases such as AIDS are a growing medical problem. A better understanding of the basic life cycle of these viruses will play an important role in the management of the diseases they cause. Physicians with both clinical and basic science expertise will be crucial to the management of these patients. The early events in the avian retroviral life cycle, from viral entry to integration, are poorly understood. Immunoprecipitation analysis, competition binding studies and prelabelled virions will be used to show that a nucleoprotein complex, derived from the incoming virion, exists in newly infected cells and establish that viral proteins are specifically associated with the nucleic acid within this complex. The time course of the formation and dissolution of the complex from viral entry until integration will be followed. The nucleoprotein complex, purified by rate zonal centrifugation and gel exclusion chromatography will be tested for integration activity using an in vitro system established in this laboratory. Indirect immunofluorescence and radiolabelled virions will be used to test the hypothesis that the nucleoprotein complex mediates nuclear transport of the nascent viral DNA. A possible viral protein nuclear localization signal will be tested. These studies will provide important insight into the basic mechanism of retroviral replication and further our understanding of all retroviral induced diseases.
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