Characterization of a putative ancestor of coxsackievirus B5

Maria Gullberg, Conny Tolf, Nina Jonsson, Mick N. Mulders, Carita Savolainen-Kopra, Tapani Hovi, Marc Van Ranst, Philippe Lemey, Susan Hafenstein, A. Michael Lindberg

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Like other RNA viruses, coxsackievirus B5 (CVB5) exists as circulating heterogeneous populations of genetic variants. In this study, we present the reconstruction and characterization of a probable ancestral virion of CVB5. Phylogenetic analyses based on capsid protein-encoding regions (the VP1 gene of 41 clinical isolates and the entire P1 region of eight clinical isolates) of CVB5 revealed two major cocirculating lineages. Ancestral capsid sequences were inferred from sequences of these contemporary CVB5 isolates by using maximum likelihood methods. By using Bayesian phylodynamic analysis, the inferred VP1 ancestral sequence dated back to 1854 (1807 to 1898). In order to study the properties of the putative ancestral capsid, the entire ancestral P1 sequence was synthesized de novo and inserted into the replicative backbone of an infectious CVB5 cDNA clone. Characterization of the recombinant virus in cell culture showed that fully functional infectious virus particles were assembled and that these viruses displayed properties similar to those of modern isolates in terms of receptor preferences, plaque phenotypes, growth characteristics, and cell tropism. This is the first report describing the resurrection and characterization of a picornavirus with a putative ancestral capsid. Our approach, including a phylogenetics-based reconstruction of viral predecessors, could serve as a starting point for experimental studies of viral evolution and might also provide an alternative strategy for the development of vaccines.

Original languageEnglish (US)
Pages (from-to)9695-9708
Number of pages14
JournalJournal of virology
Volume84
Issue number19
DOIs
StatePublished - Jan 1 2010

Fingerprint

Enterovirus
ancestry
capsid
Capsid
virion
Virion
Picornaviridae
Viruses
viruses
tropisms
Tropism
Bayes Theorem
RNA Viruses
phylogeny
vaccine development
Population Genetics
Capsid Proteins
Bayesian theory
coat proteins
population genetics

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Gullberg, M., Tolf, C., Jonsson, N., Mulders, M. N., Savolainen-Kopra, C., Hovi, T., ... Lindberg, A. M. (2010). Characterization of a putative ancestor of coxsackievirus B5. Journal of virology, 84(19), 9695-9708. https://doi.org/10.1128/JVI.00071-10
Gullberg, Maria ; Tolf, Conny ; Jonsson, Nina ; Mulders, Mick N. ; Savolainen-Kopra, Carita ; Hovi, Tapani ; Van Ranst, Marc ; Lemey, Philippe ; Hafenstein, Susan ; Lindberg, A. Michael. / Characterization of a putative ancestor of coxsackievirus B5. In: Journal of virology. 2010 ; Vol. 84, No. 19. pp. 9695-9708.
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Gullberg, M, Tolf, C, Jonsson, N, Mulders, MN, Savolainen-Kopra, C, Hovi, T, Van Ranst, M, Lemey, P, Hafenstein, S & Lindberg, AM 2010, 'Characterization of a putative ancestor of coxsackievirus B5', Journal of virology, vol. 84, no. 19, pp. 9695-9708. https://doi.org/10.1128/JVI.00071-10

Characterization of a putative ancestor of coxsackievirus B5. / Gullberg, Maria; Tolf, Conny; Jonsson, Nina; Mulders, Mick N.; Savolainen-Kopra, Carita; Hovi, Tapani; Van Ranst, Marc; Lemey, Philippe; Hafenstein, Susan; Lindberg, A. Michael.

In: Journal of virology, Vol. 84, No. 19, 01.01.2010, p. 9695-9708.

Research output: Contribution to journalArticle

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Gullberg M, Tolf C, Jonsson N, Mulders MN, Savolainen-Kopra C, Hovi T et al. Characterization of a putative ancestor of coxsackievirus B5. Journal of virology. 2010 Jan 1;84(19):9695-9708. https://doi.org/10.1128/JVI.00071-10