Study of the early-steps of the HIV replication cycle of infectious HIV particles

    Project: Research project

    Project Details

    Description

    Since the discovery of HIV 82, the study of the HIV molecular mechanisms of infection allowed the direct targeting of the virus replication. This resulted in effective anti-retroviral therapies with great outcomes to the HIV pandemic. However, without a cure there is still a need for new approaches that may have significant positive impact on HIV/AIDS. Therefore the discovery of cellular mechanisms that counteract HIV infection would be of extreme importance. Although continuous progress from the field, there are substantial gaps remaining in our understanding of these processes that are crucial to viral infection.
    The recent intense scrutiny of the early-steps of HIV infection resulted in the discovery of many cellular proteins that are involved in infection. The viral capsid structure, formed by multiple CA viral protein subunits, has been shown to be essential from fusion to the integration of the virus. Determinants in CA drive microtubule trafficking, the early-stages of reverse transcription, nuclear translocation, selection of preferential sites of HIV integration, and modulate the level of innate responses. The field intensively debates as to how the virus coordinates uncoating with these multiple steps of infection, and debates which host factors and pathways play supportive or obstructive roles. Another topic of interest is if whether these events are conserved across cell type and cellular compartments.
    As not all fused HIV particles are able to infect a cell and there are a distribution of distinct viral particles fates that occur post-fusion, it becomes therefore of importance to distinguishing between the behavior of particles that are able to infect a cell and establish a producing infection, and particles that are ineffectual and are degraded by the cell. The latter is possibly the result from the action of deleterious cellular responses. We developed a live-cell imaging method that allows distinguishing between non-infectious and infectious behavior of HIV viral particles by challenging cells with less than one particle per cell 3. We will apply these methods to study the interactions between directly labeled CA, which is incorporated into functional capsid lattices, and recombinant proteins delivered to CD4 T-cells, macrophages, and dendritic cells.
    StatusActive
    Effective start/end date9/1/197/31/21

    Funding

    • University of Utah (10044932-17//8P50AI150464-13 REVISED)
    • National Institute of Allergy and Infectious Diseases (10044932-17//8P50AI150464-13 REVISED)

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