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Characterization of the terminal regions of hepatitis C viral RNA: identification of conserved sequences in the 5' untranslated region and poly(A) tails at the 3' end.

ABSTRACT: We have determined the nucleotide sequence at the extreme 5' and 3' termini of the hepatitis C virus (HCV) genome. Our analyses of these sequences show (i) the nucleotide sequence in the 5' untranslated region is highly conserved among HCV isolates of widely varying geographical origin, (ii) within this region, there are blocks of nucleotide sequence homology with pestiviruses but not with other viruses, (iii) the relative position of short open reading frames present in the same region of the HCV genome is similar to that of the pestiviral genome, (iv) RNAs truncated at the 5' and 3' ends are found, but the origin and functions of these RNAs are unknown, and (v) poly(A) tails appear to be present on 3' subgenomic RNAs. These data differentiate HCV from the flaviviruses and indicate a closer evolutionary relationship of HCV with the pestiviruses. However, HCV also appears to be substantially different from other known pestiviruses. These data are consistent with the assignment of HCV to a separate viral genus.

SUBMITTER: Han JH

PROVIDER: S-EPMC51094 | biostudies-other | 1991 Mar

REPOSITORIES: biostudies-other

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Characterization of the terminal regions of hepatitis C viral RNA: identification of conserved sequences in the 5' untranslated region and poly(A) tails at the 3' end.

Han J H JH Shyamala V V Richman K H KH Brauer M J MJ Irvine B B Urdea M S MS Tekamp-Olson P P Kuo G G Choo Q L QL Houghton M M

Proceedings of the National Academy of Sciences of the United States of America 19910301 5

We have determined the nucleotide sequence at the extreme 5' and 3' termini of the hepatitis C virus (HCV) genome. Our analyses of these sequences show (i) the nucleotide sequence in the 5' untranslated region is highly conserved among HCV isolates of widely varying geographical origin, (ii) within this region, there are blocks of nucleotide sequence homology with pestiviruses but not with other viruses, (iii) the relative position of short open reading frames present in the same region of the H ...[more]

PMID: 1705704

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Project description:Duck Tembusu virus (DTMUV) (genus Flavivirus) is a causative agent of duck egg drop syndrome and has zoonotic potential. The positive-strand RNA genomes of flaviviruses are commonly translated in a cap-dependent manner. However, dengue and Zika viruses also exhibit cap-independent translation. In this study, we show that RNAs containing 5' and 3' untranslated regions (UTRs) of DTMUV, mosquito-borne Tembusu virus (TMUV), and Japanese encephalitis virus can be translated in a cap-independent manner in mammalian, avian, and mosquito cells. The ability of the 5' UTRs of flaviviruses to direct the translation of a second open reading frame in bicistronic RNAs was much less than that observed for internal ribosome entry site (IRES) encephalomyocarditis virus, indicating a lack of substantial IRES activity. Instead, cap-independent translation of DTMUV RNA was dependent on the presence of a 3' UTR, RNA secondary structures located in both UTRs, and specific RNA sequences. Mutations inhibiting cap-independent translation decreased DTMUV proliferation in vitro and delayed, but did not prevent, the death of infected duck embryos. Thus, the 5' and 3' UTRs of DTMUV enable the virus to use a cap- and IRES-independent RNA genome translation strategy that is important for its propagation and virulence.IMPORTANCE The genus Flavivirus includes major human pathogens, as well as animal-infecting viruses with zoonotic potential. In order to counteract the threats these viruses represent, it is important to understand their basic biology to develop universal attenuation strategies. Here, we demonstrate that five different flaviviruses use cap-independent translation, indicating that the phenomenon is probably common to all members of the genus. The mechanism used for flavivirus cap-independent translation was found to be different from that of IRES-mediated translation and dependent on both 5' and 3' UTRs that act in cis As cap-independent translation was also observed in mosquito cells, its role in flavivirus infection is unlikely to be limited to the evasion of consequences of the shutoff of host translation. We found that the inhibition of cap-independent translation results in decreased viral proliferation, indicating that the strategy could be applied to produce attenuated variants of flaviviruses as potential vaccine candidates.

Dataset Information

Characterization of the terminal regions of hepatitis C viral RNA: identification of conserved sequences in the 5' untranslated region and poly(A) tails at the 3' end.

Publications

Characterization of the terminal regions of hepatitis C viral RNA: identification of conserved sequences in the 5' untranslated region and poly(A) tails at the 3' end.

Similar Datasets

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