Behavior of HIV in Viral Environments (B-HIVE)

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ABSTRACT, OVERVIEW The Behavior of HIV In Viral Environments (B-HIVE) Center has been formed to further the understanding of HIV-1 and HIV-1/cellular host factor macromolecular interactions within distinct cellular environments, which shape the HIV replication cycle. With the limited size of HIV’s RNA genome, it is no surprise that many of the same gene products end up performing different functions in different cellular environments at different times during replication. These various HIV-1-cell host factor interactions promote the cellular pathogenesis, and ultimately disease, characteristic of HIV-1/AIDS. All members have joined the B-HIVE Center with the common goal to collaboratively investigate the dynamic HIV-1 and HIV-1/cellular host factor macromolecular interactions within distinct cellular environments that occur during infection. The B-HIVE Center will capitalize on well- established collaborations between top HIV researchers and scientific accomplishments that provide the rationale to ask new and challenging questions and will be informed by the former HIVE Center (HIV Interaction and Viral Evolution), an organizational structure proven to be effective at not only HIV-1 research, but also by exemplary communication to training, and outreach activities. The B-HIVE team of highly collaborative investigators includes well-established experts in structural, biophysical, chemical, and computational biology, virology, and synthetic chemistry. Only as a Center do the researchers have the necessary combined expertise and critical mass to effectively study the dynamic and mechanistic implications of macromolecular interactions of HIV and cellular host factors within distinct cellular environments. The overall aims of the B-HIVE are organized around three complementary Projects that focus on specific stages of the viral replication cycle: Project 1. Dynamic HIV-1 core interactions with host factors and inhibitors from cytoplasm to nucleus. Aim 1. To discover and characterize novel, dynamic interactions between HIV-1 CA and host cell during virus ingress. Aim 2. To characterize interactions of novel small molecule inhibitors with distinct sites on HIV-1 CA. Project 2. Structural dynamics of HIV-1 nuclear trafficking, integration, and transition to transcription. Aim1. Elucidate dynamic HIV-1 core-host cell interactions crucial for nuclear trafficking, uncoating, and integration. Aim 2. Define the structural and dynamic nuclear events underlying HIV-1 integration site selection. Aim 3. Determine the interplay between integration site and transcriptional latency. Project 3. The dynamics of HIV-1 packaging and assembly. Aim 1. Study the mechanism of HIV-1 RNA genome packaging and the proteins complexed with HIV-1 RNA. Aim 2. Probe the cellular dynamics of the interactions between HIV-1 Gag and identified cellular factors that alter HIV-1 production. Aim 3. Elucidate the dynamics of model Gag assembly and particle formation.