Functions and requirements of conserved RNA structures in the 3’ untranslated region of Flaviviruses

Agostinho Gonçalves Costa da Silva, P.

The Flavivirus genus contains nearly 80 viruses, including many important human pathogens such as dengue virus, yellow fever virus, West Nile virus and tick-borne encephalitis virus. To reduce and prevent the impact of flavivirus infection on society, vaccines and effective therapies are required. However, this can only be achieved by increasing our knowledge regarding fundamental aspects of the molecular biology of flaviviruses and a better understanding of the interactions between the virus, the host and the vector. Flaviviruses are small, enveloped viruses containing a positive single-stranded RNA genome of approximately 11 kb with a 5__-cap structure and a non-polyadenylated 3__ end. The flavivirus 3__ untranslated region (UTR) is known to be important for replication and translation of the viral genome. The 3__ UTR contains well conserved RNA sequences and is predicted to fold into a highly complex structure involving several stem-loops and RNA pseudoknots. Some of these motifs...Show moreThe Flavivirus genus contains nearly 80 viruses, including many important human pathogens such as dengue virus, yellow fever virus, West Nile virus and tick-borne encephalitis virus. To reduce and prevent the impact of flavivirus infection on society, vaccines and effective therapies are required. However, this can only be achieved by increasing our knowledge regarding fundamental aspects of the molecular biology of flaviviruses and a better understanding of the interactions between the virus, the host and the vector. Flaviviruses are small, enveloped viruses containing a positive single-stranded RNA genome of approximately 11 kb with a 5__-cap structure and a non-polyadenylated 3__ end. The flavivirus 3__ untranslated region (UTR) is known to be important for replication and translation of the viral genome. The 3__ UTR contains well conserved RNA sequences and is predicted to fold into a highly complex structure involving several stem-loops and RNA pseudoknots. Some of these motifs and structures have been studied in detail and attributed a biological function, although only a small fraction of the predicted structures has been confirmed by probing. The aim of this thesis was to characterize and determine the biological function of RNA elements present in the flavivirus 3__ UTR.Show less

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Functions and requirements of conserved RNA structures in the 3’ untranslated region of Flaviviruses