Secondary Structure Analysis of 5'Untranslated Region in Enterovirus D68
Advisor Information
William Tapprich
Presentation Type
Oral Presentation
Start Date
26-3-2021 12:00 AM
End Date
26-3-2021 12:00 AM
Abstract
Enterovirus D68 is a single-stranded positive-sense RNA virus of the picornaviridae family which utilizes its 5' untranslated region (5'UTR) to recruit ribosome and undergo cap-independent translation. First isolated in 1962 in California, EV-D68 only had minor cases of respiratory illness until 2014. Since the summer of 2014, reported outbreaks for EV D68 have been increasing with a strong association with polio-like acute flaccid myelitis (AFM). Ample evidence suggests that the 750 nucleotide long 5'UTR of enteroviruses includes the internal ribosome entry site (IRES) which plays an important role in determining their virulence. Neurotropic strains of EV-D68 have several point mutations on the IRES and an approximate 25 nucleotide deletion in the spacer region of their 5’UTR. Understanding the structural changes in 5'UTR of current EV D68 strains from the ones in 1962 can help determine the reason for its newly gained neurotropism. A robust secondary structure of the 5'UTR is being generated by using the SHAPE- MaP analysis. This method involves chemical modification of the 2' hydroxyl group of nucleotides in the RNA molecules based on their position and flexibility. These modified molecules are converted into cDNA to create high-quality mutational profiles (MaP), which are then subjected to massively parallel sequencing. By using computational tools like the shapemapper2 and superfold to analyze the NGS data, a secondary structure of the 5'UTR can be generated. Elucidating novel 5'UTR secondary structures of EV D68- Fermon (1962) and EV D68- KT347251.2 (2014) strains can reveal the structural changes leading to neurotropism. These novel structures of 5'UTRs in different strains of EVD68 can also be utilized for comparative studies of 5’UTRs between other neurotropic enteroviruses like EV 71- KF312457.1 (1998), Polio Virus, and non-neurotropic enteroviruses like CVB3 to find key shared structures involved in determining the virulence of enteroviruses.
Scheduling Link
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Secondary Structure Analysis of 5'Untranslated Region in Enterovirus D68
Enterovirus D68 is a single-stranded positive-sense RNA virus of the picornaviridae family which utilizes its 5' untranslated region (5'UTR) to recruit ribosome and undergo cap-independent translation. First isolated in 1962 in California, EV-D68 only had minor cases of respiratory illness until 2014. Since the summer of 2014, reported outbreaks for EV D68 have been increasing with a strong association with polio-like acute flaccid myelitis (AFM). Ample evidence suggests that the 750 nucleotide long 5'UTR of enteroviruses includes the internal ribosome entry site (IRES) which plays an important role in determining their virulence. Neurotropic strains of EV-D68 have several point mutations on the IRES and an approximate 25 nucleotide deletion in the spacer region of their 5’UTR. Understanding the structural changes in 5'UTR of current EV D68 strains from the ones in 1962 can help determine the reason for its newly gained neurotropism. A robust secondary structure of the 5'UTR is being generated by using the SHAPE- MaP analysis. This method involves chemical modification of the 2' hydroxyl group of nucleotides in the RNA molecules based on their position and flexibility. These modified molecules are converted into cDNA to create high-quality mutational profiles (MaP), which are then subjected to massively parallel sequencing. By using computational tools like the shapemapper2 and superfold to analyze the NGS data, a secondary structure of the 5'UTR can be generated. Elucidating novel 5'UTR secondary structures of EV D68- Fermon (1962) and EV D68- KT347251.2 (2014) strains can reveal the structural changes leading to neurotropism. These novel structures of 5'UTRs in different strains of EVD68 can also be utilized for comparative studies of 5’UTRs between other neurotropic enteroviruses like EV 71- KF312457.1 (1998), Polio Virus, and non-neurotropic enteroviruses like CVB3 to find key shared structures involved in determining the virulence of enteroviruses.