Molecular interactions at the host-virus interface
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Molecular interactions govern the structure and function of most biological systems. The investigation of molecular interactions is therefore fundamental to the advancement of health-related scientific fields. Virology represents a field where unique molecular interactions have been developed over millions of years of co-evolution between viruses and hosts. While investigation of the host-virus interface has been ongoing for over 100 years, the fast mutation rate of viruses and their ability to modulate their hosts makes the host-virus interface fluid and expanding. In this collection of works, we aim to refine the view of the HIV-1-host interface and develop new reagents and systems to analyze the host-virus interface. Through CRISPR/Cas9 screening using HIV-1 induced death as a partition, we identified JunB as a modulator of HIV-1 co-receptor CXCR4, therefore protecting cells from HIV-1 infection. We then identify molecular interactions of RNA aptamers in complex with the HIV-1 capsid protein. Understanding the impact of aptamer binding on capsid structure is critical to the appropriate deployment of the aptamers as reagents to study the host-virus interface. Finally, we develop a system to measure innate immune signaling in a model system using dsRNA sensors TLR3 and RIG-I and demonstrated a selection method for PRR binding RNAs, offering opportunities for innate immune antagonism and activation. Results presented within this dissertation drive scientific progress through deeper understanding of underlying molecular interactions.
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Ph. D.