Our Center for the Structural Biology of Cellular Host Elements in Egress, Trafficking, and Assembly of HIV (CHEETAH) studies HIV-Host interactions involved in viral replication, trafficking and transmission. Our studies focus on four key aspects of HIV-1 biology: 1) HIV assembly and host budding restrictions, 2) HIV transmission in whole animals and in vitro models, 3) Intracellular trafficking, transformations and restriction of the viral core, and 4) New directions in viral latency and immune receptors. In each case, we aim to understand: 1) The relevant molecular machines, 2) The mechanisms by which host pathways are recruited and utilized, and 3) The structures of underlying tissues, cellular assemblies, and viral components. Two other overarching themes of the Center are: 1) Studies of dynamic processes, ranging from key molecular transformations in the viral life cycle to studies of virus transmission and dissemination in whole animals, and 2) Developing and applying complementary approaches for studying viral and cellular structures across a range of resolutions, spatial and temporal dimensions, and biological contexts. In parallel, we are developing and applying tools that will advance important frontiers in structural biology and HIV molecular virology, including: 1) New approaches for transforming cryo-EM reconstructions, 2) Correlated light and electron cryotomography (CLEM-ECT) approaches for visualizing viral complexes inside cells, 3) Imaging HIV transmission in humanized mice and primate tissues, and 4) Designing new proteins that can mimic viral assembly, release, and entry. All of these efforts are supported by state-of-the-art Cores for: 1) Producing biological reagents, 2) Performing structural biology, 3) Spectroscopy and imaging, 4) Computation and data science, and 5) Biological models. The efforts of our Center are also extended through: 1) Extensive collaborations with other researchers and P50 Centers, 2) A Collaborative Development Awards program that will fund promising young investigators who will enhance and benefit from interactions with our Center, and 3) Educational programs for Center trainees. Our overall goals are to continue to develop HIV into an unparalleled model system for studying how a human virus interacts with its host, and to lay the groundwork for the development of new antiviral therapies.
Like other viruses, HIV-1 makes extensive use of host factors and pathways as it traffics through the body and the cell, and undergoes major transformations during each stage of its viral life cycle. These virus-host interfaces are, in principle, attractive targets for therapeutic intervention. Our CHEETAH Center will help to realize this promise by providing a more comprehensive understanding of the structures, mechanisms, and functions of critical host-virus interactions.
|Wang, Haoqing; Barnes, Christopher O; Yang, Zhi et al. (2018) Partially Open HIV-1 Envelope Structures Exhibit Conformational Changes Relevant for Coreceptor Binding and Fusion. Cell Host Microbe 24:579-592.e4|
|Pastuzyn, Elissa D; Day, Cameron E; Kearns, Rachel B et al. (2018) The Neuronal Gene Arc Encodes a Repurposed Retrotransposon Gag Protein that Mediates Intercellular RNA Transfer. Cell 172:275-288.e18|
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|Pak, Alexander J; Voth, Gregory A (2018) Advances in coarse-grained modeling of macromolecular complexes. Curr Opin Struct Biol 52:119-126|
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|Shepherd, Jason D (2018) Arc - An endogenous neuronal retrovirus? Semin Cell Dev Biol 77:73-78|
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