The 3′ untranslated region of tick-borne flaviviruses originated by the duplication of long repeat sequences within the open reading frame

Грицун, Т.С.; Gould, Ernest A.

doi:10.1016/j.virol.2006.03.002

Cited by 19 publications

(22 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The alignment and corresponding predicted RNA structures (Figure 1, Figures S1 and S2) were annotated with previously identified linear nucleotide motifs that include: 1) LRSs1–6 and short direct repeats (DRs1–6) [16]; 2) variable V3′UTR and conserved C3′UTR regions [24], [25] and 3) boundaries between promoter and enhancer regions [11], [12], [14]. TBFV promoter and enhancer regions have been established empirically as essential and redundant regions for virus replication in tissue culture [15], [26].…”

Section: Resultsmentioning

confidence: 99%

Molecular Archaeology of Flaviviridae Untranslated Regions: Duplicated RNA Structures in the Replication Enhancer of Flaviviruses and Pestiviruses Emerged via Convergent Evolution

Gritsun

Jones

Gould³

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

RNA secondary structures in the 3′untranslated regions (3′UTR) of the viruses of the family Flaviviridae, previously identified as essential (promoters) or beneficial (enhancers) for replication, have been analysed. Duplicated enhancer elements are revealed as a global feature in the evolution of the 3′UTR of distantly related viruses within the genera Flavivirus and Pestivirus. For the flaviviruses, duplicated structures occur in the 3′UTR of all four distantly related ecological virus subgroups (tick-borne, mosquito-borne, no known vector and insect-specific flaviviruses (ISFV). RNA structural differences distinguish tick-borne flaviviruses with discrete pathogenetic characteristics. For Aedes- and Culex-associated ISFV, secondary RNA structures with different conformations display numerous short ssRNA direct repeats, exposed as loops and bulges. Long quadruplicate regions comprise almost the entire 3′UTR of Culex-associated ISFV. Extended duplicated sequence and associated RNA structures were also discovered in the 3′UTR of pestiviruses. In both the Flavivirus and Pestivirus genera, duplicated RNA structures were localized to the enhancer regions of the 3′UTR suggesting an adaptive role predominantly in wild-type viruses. We propose sequence reiteration might act as a scaffold for dimerization of proteins involved in assembly of viral replicase complexes. Numerous nucleotide repeats exposed as loops/bulges might also interfere with host immune responses acting as a molecular sponge to sequester key host proteins or microRNAs.

show abstract

Section: Resultsmentioning

confidence: 99%

Molecular Archaeology of Flaviviridae Untranslated Regions: Duplicated RNA Structures in the Replication Enhancer of Flaviviruses and Pestiviruses Emerged via Convergent Evolution

Gritsun

Jones

Gould³

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Investigations of the function and evolution of 3′UTRs in arboviruses, including repeat identifications [9], [10], [13] and secondary structure predictions [12], [14], [38], as well as experimental studies [3]–[8], [39], [40], have taken place for many years. However, ongoing positive selection on the 3′UTR has never been observed in ‘real-time,’ and the role of the 3′UTR remains poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…Basically, sequence duplications and deletions, in contrast to point mutations that are predominant in ORFs, are the major evolution mechanisms of flavivirus 3′UTRs [12]. Interestingly, the ORF region adjacent to the flavivirus 3′UTR [13], as well as 5′UTR panhandle structure [46], may also have originated from duplications of 3′ long repeat sequences (LRS). Furthermore, conserved secondary structures have been observed in the 3′UTRs of all eco-groups of flaviviruses [14].…”

Section: Discussionmentioning

confidence: 99%

“…These DRs can be relatively conserved in closely related viruses, indicating that repeat duplication may serve as a major evolutionary mechanism for the 3′UTR, and that these DRs may have functional significance. Indeed, sequence comparisons of flaviviruses suggest that duplication of long repeat elements (LREs) and extensive deletions are the main evolutionary mechanisms of the 3′UTR [12], [13]. Despite their high level of sequence diversity, secondary structure predictions suggest that the flavivirus 3′UTR comprises enriched stem-loop structures, with some conserved structural motifs observed in all species, suggesting functional selection [14].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Chikungunya Virus 3′ Untranslated Region: Adaptation to Mosquitoes and a Population Bottleneck as Major Evolutionary Forces

et al. 2013

View full text Add to dashboard Cite

The 3′ untranslated genome region (UTR) of arthropod-borne viruses is characterized by enriched direct repeats (DRs) and stem-loop structures. Despite many years of theoretical and experimental study, on-going positive selection on the 3′UTR had never been observed in ‘real-time,’ and the role of the arbovirus 3′UTR remains poorly understood. We observed a lineage-specific 3′UTR sequence pattern in all available Asian lineage of the mosquito-borne alphavirus, chikungunya virus (CHIKV) (1958–2009), including complicated mutation and duplication patterns of the long DRs. Given that a longer genome is usually associated with less efficient replication, we hypothesized that the fixation of these genetic changes in the Asian lineage 3′UTR was due to their beneficial effects on adaptation to vectors or hosts. Using reverse genetic methods, we examined the functional importance of each direct repeat. Our results suggest that adaptation to mosquitoes, rather than to mammalian hosts, is a major evolutionary force on the CHIKV 3′UTR. Surprisingly, the Asian 3′UTR appeared to be inferior to its predicted ancestral sequence for replication in both mammals and mosquitoes, suggesting that its fixation in Asia was not a result of directional selection. Rather, it may have resulted from a population bottleneck during its introduction from Africa to Asia. We propose that this introduction of a 3′UTR with deletions led to genetic drift and compensatory mutations associated with the loss of structural/functional constraints, followed by two independent beneficial duplications and fixation due to positive selection. Our results provide further evidence that the limited epidemic potential of the Asian CHIKV strains resulted from founder effects that reduced its fitness for efficient transmission by mosquitoes there.

show abstract

“…TBEV contains an ∼11 kb positive sense, single-stranded RNA genome encoding a single polyprotein, flanked by the 5′- and 3′- non-coding regions (NCRs). The polyprotein is processed into three structural proteins: capsid (C), membrane (prM), and envelope (E), and seven non-structural (NS) proteins: NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5 [6], [7]. The 5′NCR is highly conserved, whereas the 3′NCR can be divided into a conserved core element (C 3′NCR) and a variable part (V 3′NCR) [8], [9].…”

Section: Introductionmentioning

confidence: 99%

Tick-Borne Encephalitis Virus Sequenced Directly from Questing and Blood-Feeding Ticks Reveals Quasispecies Variance

et al. 2014

View full text Add to dashboard Cite

The increased distribution of the tick-borne encephalitis virus (TBEV) in Scandinavia highlights the importance of characterizing novel sequences within the natural foci. In this study, two TBEV strains: the Norwegian Mandal 2009 (questing nymphs pool) and the Swedish Saringe 2009 (blood-fed nymph) were sequenced and phylogenetically characterized. Interestingly, the sequence of Mandal 2009 revealed the shorter form of the TBEV genome, similar to the highly virulent Hypr strain, within the 3′ non-coding region (3′NCR). A different genomic structure was found in the 3′NCR of Saringe 2009, as in-depth analysis demonstrated TBEV variants with different lengths within the poly(A) tract. This shows that TBEV quasispecies exists in nature and indicates a putative shift in the quasispecies pool when the virus switches between invertebrate and vertebrate environments. This prompted us to further sequence and analyze the 3′NCRs of additional Scandinavian TBEV strains and control strains, Hypr and Neudoerfl. Toro 2003 and Habo 2011 contained mainly a short (A)3C(A)6 poly(A) tract. A similar pattern was observed for the human TBEV isolates 1993/783 and 1991/4944; however, one clone of 1991/4944 contained an (A)3C(A)11 poly(A) sequence, demonstrating that quasispecies with longer poly(A) could be present in human isolates. Neudoerfl has previously been reported to contain a poly(A) region, but to our surprise the re-sequenced genome contained two major quasispecies variants, both lacking the poly(A) tract. We speculate that the observed differences are important factors for the understanding of virulence, spread, and control of the TBEV.

show abstract

The 3′ untranslated region of tick-borne flaviviruses originated by the duplication of long repeat sequences within the open reading frame

Cited by 19 publications

References 22 publications

Molecular Archaeology of Flaviviridae Untranslated Regions: Duplicated RNA Structures in the Replication Enhancer of Flaviviruses and Pestiviruses Emerged via Convergent Evolution

Molecular Archaeology of Flaviviridae Untranslated Regions: Duplicated RNA Structures in the Replication Enhancer of Flaviviruses and Pestiviruses Emerged via Convergent Evolution

Chikungunya Virus 3′ Untranslated Region: Adaptation to Mosquitoes and a Population Bottleneck as Major Evolutionary Forces

Tick-Borne Encephalitis Virus Sequenced Directly from Questing and Blood-Feeding Ticks Reveals Quasispecies Variance

Contact Info

Product

Resources

About