Genomics and evolution of Aedes-borne flaviviruses

Grard, Gilda; Moureau, Grégory; Charrel, Rémi N.; Holmes, Edward C.; Gould, Ernest A.; Lamballerie, Xavier de

doi:10.1099/vir.0.014506-0

Cited by 78 publications

(70 citation statements)

References 28 publications

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“…The DCS-PK element is located in the capsid-coding region of DENV and Culexborne flaviviruses, but not YFV. This finding agrees with a phylogenetics study (52) that indicated that the YFV group diverged early and evolved independently, whereas DENV and Culexborne flaviviruses are closer in evolution. The recently identified tick-borne flavivirus SL6 element (27) shares homology with stem 1 of DCS-PK; however, these two elements are likely to modulate vRNA replication by distinct mechanisms.…”

Section: Discussionsupporting

confidence: 83%

Novel cis -Acting Element within the Capsid-Coding Region Enhances Flavivirus Viral-RNA Replication by Regulating Genome Cyclization

Liu

Jiang

et al. 2013

J Virol

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c cis-Acting elements in the viral genome RNA (vRNA) are essential for the translation, replication, and/or encapsidation of RNA viruses. In this study, a novel conserved cis-acting element was identified in the capsid-coding region of mosquito-borne flavivirus. The downstream of 5= cyclization sequence (5=CS) pseudoknot (DCS-PK) element has a three-stem pseudoknot structure, as demonstrated by structure prediction and biochemical analysis. Using dengue virus as a model, we show that DCS-PK enhances vRNA replication and that its function depends on its secondary structure and specific primary sequence. Mutagenesis revealed that the highly conserved stem 1 and loop 2, which are involved in potential loop-helix interactions, are crucial for DCS-PK function. A predicted loop 1-stem 3 base triple interaction is important for the structural stability and function of DCS-PK. Moreover, the function of DCS-PK depends on its position relative to the 5=CS, and the presence of DCS-PK facilitates the formation of 5=-3= RNA complexes. Taken together, our results reveal that the cis-acting element DCS-PK enhances vRNA replication by regulating genome cyclization, and DCS-PK might interplay with other cis-acting elements to form a functional vRNA cyclization domain, thus playing critical roles during the flavivirus life cycle and evolution. T he flavivirus genus contains numerous important agents of human infectious diseases, including dengue virus (DENV), West Nile virus (WNV), Japanese encephalitis virus (JEV), yellow fever virus (YFV), and tick-borne encephalitis virus (TBEV). Human infection by flaviviruses can result in symptoms ranging from mild fever to severe encephalitis and hemorrhagic fever. Due to lack of effective vaccines and specific medicines against many flaviviruses, they pose a significant threat to human health around the world.Flaviviruses are enveloped RNA viruses with single-stranded, positive-sense genomes. Their 5= capped viral genome RNA (vRNA) is approximately 10 to 11 kb and contains a single open reading frame (ORF) flanked by 5= and 3= untranslated regions (UTRs). The ORF encodes a polyprotein with more than 3,000 residues, which is cotranslationally and/or posttranslationally proteolytically processed into three structural proteins (capsid, pre-membrane/membrane, and envelope) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) by viral and cellular proteases. NS3 and NS5 perform essential enzyme activities required for vRNA replication. The C-terminal domain of NS3 has helicase/NTPase (1) and RNA triphosphatase activities (2, 3). The N-terminal domain of NS5 encodes guanylyltransferase (4) and methyltransferase activities (5, 6), whereas the C-terminal domain of NS5 has RNA-dependent RNA polymerase (RdRp) activity. These enzyme activities are involved in vRNA synthesis, 5= capping, and internal adenosine methylation (7).The 5=UTR, 3=UTR, and capsid-coding sequence are involved in vRNA replication, translation, and perhaps encapsidation, and many cis-acting elements have ...

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Section: Discussionsupporting

confidence: 83%

Novel cis -Acting Element within the Capsid-Coding Region Enhances Flavivirus Viral-RNA Replication by Regulating Genome Cyclization

Liu

Jiang

et al. 2013

J Virol

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“…Sources used to identify host species included, but were not limited to, GenBank host and reference entries accompanying sequence data, the ICTVdB (http://www. ictvonline.org/), Grard et al (28), Kuzmin et al (29), and Tidona and Darai (30). Reservoir hosts for some viruses included in this study could not be identified with confidence.…”

Section: Methodsmentioning

confidence: 99%

Family level phylogenies reveal modes of macroevolution in RNA viruses

Kitchen

Shackelton

Holmes

2010

Proc. Natl. Acad. Sci. U.S.A.

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Despite advances in understanding the patterns and processes of microevolution in RNA viruses, little is known about the determinants of viral diversification at the macroevolutionary scale. In particular, the processes by which viral lineages assigned as different "species" are generated remain largely uncharacterized. To address this issue, we use a robust phylogenetic approach to analyze patterns of lineage diversification in five representative families of RNA viruses. We ask whether the process of lineage diversification primarily occurs when viruses infect new host species, either through cross-species transmission or codivergence, and which are defined here as analogous to allopatric speciation in animals, or by acquiring new niches within the same host species, analogous to sympatric speciation. By mapping probable primary host species onto family level viral phylogenies, we reveal a strong clustering among viral lineages that infect groups of closely related host species. Although this is consistent with lineage diversification within individual hosts, we argue that this pattern more likely represents strong biases in our knowledge of viral biodiversity, because we also find that better-sampled human viruses rarely cluster together. Hence, although closely related viruses tend to infect related host species, it is unlikely that they often infect the same host species, such that evolutionary constraints hinder lineage diversification within individual host species. We conclude that the colonization of new but related host species may represent the principle mode of macroevolution in RNA viruses.emergence | molecular evolution | host jumping

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“…Early antigenic analyses placed KOKV and STRV in the Japanese encephalitis virus (JEV) serogroup (Calisher et al, 1989;De Madrid & Porterfield, 1974), but partial sequencing of the genome of these viruses resulted in their classification into a separate virus group (Kuno et al, 1998). Indeed, these viruses were shown to be phylogenetically closer to the Aroa group of viruses than to the JEV group (Cook & Holmes, 2006;Gaunt et al, 2001;Grard et al, 2010;Hall et al, 1991;Kuno et al, 1998;Poidinger et al, 1996).…”

mentioning

confidence: 99%

Genetic divergence among members of the Kokobera group of flaviviruses supports their separation into distinct species

May

Clark

Pham

et al. 2013

Journal of General Virology

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The Kokobera virus group comprises mosquito-borne flaviviruses that cluster together phylogenetically. These viruses are unique to Australia and Papua New Guinea, and have been associated with a mild polyarticular disease in humans. Recent isolation of genetically diverse viruses within this group has prompted analysis of their genetic and phenotypic relationships. Phylogenetic analysis based on complete ORF, the envelope gene or the NS5/3′ untranslated region supported the separation of the group into distinct species: Kokobera virus (KOKV), Stratford virus, New Mapoon virus, MK7979 and TS5273. Virulence studies in 3-week-old mice also provided the first evidence that a member of the KOKV group (MK7979) was neuroinvasive after intraperitoneal inoculation. In this context, our recent detection of KOKV group-specific antibodies in horses in the field suggests that these viruses should be considered in the epidemiology of flavivirus encephalitis in Australia.

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Genomics and evolution of Aedes-borne flaviviruses

Cited by 78 publications

References 28 publications

Novel cis -Acting Element within the Capsid-Coding Region Enhances Flavivirus Viral-RNA Replication by Regulating Genome Cyclization

Novel cis -Acting Element within the Capsid-Coding Region Enhances Flavivirus Viral-RNA Replication by Regulating Genome Cyclization

Family level phylogenies reveal modes of macroevolution in RNA viruses

Genetic divergence among members of the Kokobera group of flaviviruses supports their separation into distinct species

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