Much progress has been made over the past 20 years in understanding the molecular details of HIV biology.Through the research efforts of many laboratories the process of HIV fusion, reverse transcription,integration, the transcriptional and posttranscriptional regulation of HIV gene expression, and viral assemblyhave been well defined. In contrast, the post-fusion aspects of the HIV lifecycle are less well understood.Clearly, this is a complex area of HIV biology because number of defects in HIV proteins lead to a similarphenotype; reverse transcription is apparently initiated, yet reverse transcription is not completed or theorovirus is destabilized. Four years ago my laboratory received support to a system that would use themethods of cell biology to study the intracellular trafficking of HIV. The cornerstone of this approach was theincorporation of a fluorescent protein tag into virions utilizing a GFP-Vpr fusion protein. This allowedndividual virion and cytoplasmic HIV complexes to be fluorescently identified. Analyzing HIV cytoplasmiccomplexes revealed new details of the trafficking and biology of the viral genome as translocates to thenucleus. We were even able to obtain electron microscope images of reverse tracscription complexes usingthe fluorescent signal to reveal the cytoplasmic localization of the HIV genome. The studies proposed hereseek to build upon our success in developing a cell biological approach to study the biology of HIV betweenusion and integration. These studies, based on a cell biological approach, will continue to shed light on thisvague aspect of HIV biology. A better understanding of this segment of the viral life cycle may revealnewargets for specific antiviral therapies^
|Effective start/end date||3/1/06 → 2/28/13|
- National Institute of Allergy and Infectious Diseases (R01 AI047770)
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