5′ and 3′ untranslated regions of pestivirus genome: primary and secondary structure analyses

Abstract

Within the conserved 5' untranslated region (UTR) of the pestivirus genome three highly variable regions were identified. Preceding the polyprotein start codon, multiple cryptic AUG codons and several small open reading frames are characteristic for all the five pestiviruses. Inspection of the context of AUGs revealed that the polyprotein initiation AUG of pestivirus has a weak context for efficient translation initiation. The most favorable context was found in two of the cryptic AUGs. Two oligopyrimidine-rich tracts upstream to the conserved either cryptic or authentic AUG in the 5'-UTR of pestivirus were identified and 83.3% of their nucleotide sequences are complementary to the consensus sequence at the 3' terminus of eucaryotic 18S rRNA. A secondary structure model for the 5'-UTR of pestivirus was predicted. Nucleotide sequence comparison among five pestiviruses led to the identification of a variable region and a conserved region in the 3'-UTR. A deletion of 41 nucleotides was found within the variable region in Osloss. A secondary structure model for the 3'-UTR was also predicted. The structural similarity of the 5'-UTR between pestiviruses and picornaviruses and hepatitis C viruses was demonstrated and the possible implications of features of the 5' and 3'-UTR of pestiviruses are discussed.

Genetic typing of bovine viral diarrhoea virus in cattle on Irish farms

“…The finding of two highly variable regions identified within the 5'UTR of Irish isolates aligned in this study is in agreement with the studies by Vilcek et al (1997a) and Graham et al (2001). In addition to this, both variable regions reported in this study were consistent with the findings of Deng and Brock's (1993) investigation into the primary structures of Pestivirus 5'UTR's.…”

cis-acting RNA elements required for replication of bovine viral diarrhea virus–hepatitis C virus 5′ nontranslated region chimeras

“…The Flavivirdae is an important family of human and animal RNA viral pathogens + Virus particles consist of a lipid bilayer envelope with embedded transmembrane glycoproteins surrounding a protein-RNA nucleocapsid+ Genome RNAs are single-stranded, of positive polarity, and function as the sole mRNA species for translation of a single long open reading frame (ORF)+ Mature viral proteins are produced by co-and posttranslational processing of the resulting polyprotein by the action of cellular and viral proteases+ Structural proteins destined for incorporation into virus particles are encoded in the N-terminal portion of the polyprotein with the nonstructural proteins which form components of the viral RNA replicase being encoded in the remainder+ RNA replication occurs via synthesis of a full-length negative-strand intermediate and is asymmetic, favoring synthesis of positive-strand RNAs+ Besides these common features, the three currently recognized genera of the Flaviviridae exhibit distinct differences in transmission, host range, and pathogenesis+ Members of the classical flavivirus genus, such as yellow fever virus and dengue virus, are typically transmitted to vertebrate hosts via arthropod vectors and cause acute self-limiting disease (Monath & Heinz, 1996)+ The pestiviruses, such as bovine viral diarrhea virus (BVDV) and classical swine fever virus (CSFV), cause economically important livestock disease and are spread by direct contact or the fecal-oral route (Thiel et al+, 1996)+ The most recently characterized member of this family is the common and exclusively human pathogen, hepatitis C virus (HCV)+ HCV, the sole member of the hepacivirus genus, is transmitted by contaminated blood or blood products and is the most common agent of non-A, non-B hepatitis, affecting more that 1% of the population worldwide (Houghton, 1996)+ Unlike flavivirus and pestivirus infections, which are usually eliminated by host immune response, chronic HCV infections are common and can cause mild to severe liver disease including cancer+ Despite the importance of this virus family, little is known about the details of how RNA replication occurs+ For all three genera, full-length functional cDNA clones have been constructed and RNAs transcribed from these cDNA templates are infectious )+ For flaviviruses and pestiviruses, mutagenesis of these clones and efficient RNA transfection of permissive cell cultures provides a means of probing the role of cis RNA elements and viral proteins in replicase assembly and function+ Such analyses are not yet possible for HCV since this virus is unable to replicate efficiently in cell culture+ Like many other RNA viruses (Huang, 1997), the 59 and 39 terminal sequences of the Flaviviridae are thought to contain conserved cis-elements important for translation, RNA replication, and packaging (Bukh et al+, 1992;Deng & Brock, 1993;Cahour et al+, 1995;Kolykhalov et al+, 1996;Men et al+, 1996;Tanaka et al+, 1996;Mandl et al+, 1998)+ The 59 nontranslated region (NTR) functions initially at the level of translation+ Similar to most cellular mRNAs, flavivirus genome RNAs are translated in a cap-dependent manner+ These RNAs contain a 59 cap s...…”

Species characterization in the genus Pestivirus according to palindromic nucleotide substitutions in the 5′-untranslated region

“…In Pestiviruses, the secondary structure of the 5'-UTR includes an internal ribosomal entry site (IRES), responsible for translational, transcriptional and replicational events (Deng and Brock, 1993). Thus, stable nucleotide variations at this level assume great importance in terms of virus evolutionary history.…”