We study the mechanisms of picornavirus replication and their interactions with the host cell. In this proposal, we employ poliovirus as our model organism and focus on the ribonucleoprotein (RNP) complexes formed around the 5' and 3' ends of the viral genome. These complexes participate in both viral translation and RNA replication. Several viral and cellular proteins participate in RNP complex formation but their specific roles and functions are poorly understood. To better understand these RNP complexes, we hereby propose to study their structural characteristics and their function in the poliovirus replication cycle. To determine the functional role of these complexes we will employ complementary approaches. First, we will use a cell-free system derived from HeLa cells that supports poliovirus replication. In addition, we will use a heterologous system based on microinjection of viral RNA into Xenopus oocytes. Finally, we will use double-stranded mediated RNA interference (RNAi) as a system to deplete cellular factors involved in poliovirus replication in intact cells. The elucidation of the mechanism of poliovirus replication is likely to contribute to our general understanding of viral RNA replication. Furthermore, the identification of cellular factors involved in viral RNA replication may shed light on the role of these factors in normal cellular processes. Finally, as the poliovirus eradication campaign progresses to its conclusion it would be important to discover ways to control viral replication in case of re-emergence of the virus. These studies may yield new ways to rationally design anti-poliovirus drugs.
| Dolan, Patrick T; Whitfield, Zachary J; Andino, Raul (2018) Mapping the Evolutionary Potential of RNA Viruses. Cell Host Microbe 23:435-446 |
| Lidsky, Peter V; Lukyanov, Konstantin A; Misra, Tvisha et al. (2018) A genetically encoded fluorescent probe for imaging of oxygenation gradients in living Drosophila. Development 145: |
| Geller, Ron; Pechmann, Sebastian; Acevedo, Ashley et al. (2018) Hsp90 shapes protein and RNA evolution to balance trade-offs between protein stability and aggregation. Nat Commun 9:1781 |
| Xiao, Yinghong; Dolan, Patrick Timothy; Goldstein, Elizabeth Faul et al. (2017) Poliovirus intrahost evolution is required to overcome tissue-specific innate immune responses. Nat Commun 8:375 |
| Lidsky, Peter V; Andino, Raul; Rouzine, Igor M (2017) Variability in viral pathogenesis: modeling the dynamic of acute and persistent infections. Curr Opin Virol 23:120-124 |
| Menéndez-Arias, Luis; Andino, Raul (2017) Viral polymerases. Virus Res 234:1-3 |
| Whitfield, Zachary J; Dolan, Patrick T; Kunitomi, Mark et al. (2017) The Diversity, Structure, and Function of Heritable Adaptive Immunity Sequences in the Aedes aegypti Genome. Curr Biol 27:3511-3519.e7 |
| Stern, Adi; Yeh, Ming Te; Zinger, Tal et al. (2017) The Evolutionary Pathway to Virulence of an RNA Virus. Cell 169:35-46.e19 |
| Andino, Raul; Diamond, Michael (2017) Editorial overview: Viral pathogenesis: Strategies for virus survival - Acute versus persistent infections. Curr Opin Virol 23:v |
| Xiao, Yinghong; Rouzine, Igor M; Bianco, Simone et al. (2017) RNA Recombination Enhances Adaptability and Is Required for Virus Spread and Virulence. Cell Host Microbe 22:420 |
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