RNA Recombination Plays a Major Role in Genomic Change during Circulation of Coxsackie B Viruses

ABSTRACT RNA recombination has been shown to occur during circulation of enteroviruses, but most studies have focused on poliovirus. To examine the role of recombination in the evolution of the coxsackie B viruses (CVB), we determined the partial sequences of four genomic intervals for multiple clinical isolates of each of the six CVB serotypes isolated from 1970 to 1996. The regions sequenced were the 5′-nontranslated region (5′-NTR) (350 nucleotides [nt]), capsid (VP4-VP2, 416 nt, and VP1, ∼320 nt), and polymerase (3D, 491 nt). Phylogenetic trees were constructed for each genome region, using the clinical isolate sequences and those of the prototype strains of all 65 enterovirus serotypes. The partial VP1 sequences of each CVB serotype were monophyletic with respect to serotype, as were the VP4-VP2 sequences, in agreement with previously published studies. In some cases, however, incongruent tree topologies suggested that intraserotypic recombination had occurred between the sequenced portions of VP2 and VP1. Outside the capsid region, however, isolates of the same serotype were not monophyletic, indicating that recombination had occurred between the 5′-NTR and capsid, the capsid and 3D, or both. Almost all clinical isolates were recombinant relative to the prototype strain of the same serotype. All of the recombination partners appear to be members of human enterovirus species B. These results suggest that recombination is a frequent event during enterovirus evolution but that there are genetic restrictions that may influence recombinational compatibility.

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Recombination in circulating Human enterovirus B: independent evolution of structural and non-structural genome regions

Journal of General Virology ◽

10.1099/vir.0.81264-0 ◽

2005 ◽

Vol 86 (12) ◽

pp. 3281-3290 ◽

Cited By ~ 112

Author(s):

Alexander N. Lukashev ◽

Vasilii A. Lashkevich ◽

Olga E. Ivanova ◽

Galina A. Koroleva ◽

Ari E. Hinkkanen ◽

...

Keyword(s):

Soviet Union ◽

Former Soviet Union ◽

Phylogenetic Trees ◽

Human Enterovirus ◽

Structural Protein ◽

Genome Region ◽

3D Genome ◽

Independent Evolution ◽

Efficient Detection ◽

Recombination Hot Spots

The complete nucleotide sequences of eight Human enterovirus B (HEV-B) strains were determined, representing five serotypes, E6, E7, E11, CVB3 and CVB5, which were isolated in the former Soviet Union between 1998 and 2002. All strains were mosaic recombinants and only the VP2–VP3–VP1 genome region was similar to that of the corresponding prototype HEV-B strains. In seven of the eight strains studied, the 2C–3D genome region was most similar to the prototype E30, EV74 and EV75 strains, whilst the remaining strain was most similar to the prototype E1 and E9 strains in the non-structural protein genome region. Most viruses also bore marks of additional recombination events in this part of the genome. In the 5′ non-translated region, all strains were more similar to the prototype E9 than to other enteroviruses. In most cases, recombination mapped to the VP4 and 2ABC genome regions. This, together with the star-like topology of the phylogenetic trees for these genome regions, identified these genome parts as recombination hot spots. These findings further support the concept of independent evolution of enterovirus genome fragments and indicate a requirement for more advanced typing approaches. A range of available phylogenetic methods was also compared for efficient detection of recombination in enteroviruses.

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Enterovirus infections

Oxford Textbook of Medicine ◽

10.1093/med/9780199204854.003.070508_update_002 ◽

2010 ◽

pp. 527-536

Author(s):

Philip Minor ◽

Ulrich Desselberger

Keyword(s):

Rna Viruses ◽

Oral Route ◽

Human Enterovirus ◽

Temperate Climate ◽

Sequence Comparisons ◽

Tropical Regions ◽

Positive Sense ◽

Coxsackie B Viruses ◽

Coxsackie B

Enteroviruses are single-stranded, positive sense RNA viruses comprising poliomyelitis viruses (3 types), Coxsackie A viruses (23 types), Coxsackie B viruses (6 types), and echoviruses (33 types). They have recently been reclassified into 4 human enterovirus species (A–D) on the basis of sequence comparisons. Transmission is by the faeco-oral route, with marked seasonal peaks of infection in areas of temperate climate, but infections occurring all year round in tropical regions....

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Evidence for Frequent Recombination within Species Human Enterovirus B Based on Complete Genomic Sequences of All Thirty-Seven Serotypes

Journal of Virology ◽

10.1128/jvi.78.2.855-867.2004 ◽

2004 ◽

Vol 78 (2) ◽

pp. 855-867 ◽

Cited By ~ 173

Author(s):

M. Steven Oberste ◽

Kaija Maher ◽

Mark A. Pallansch

Keyword(s):

Complete Genome ◽

Phylogenetic Analyses ◽

Human Enterovirus ◽

Bootstrap Support ◽

Common Mechanism ◽

Rna Recombination ◽

Sequence Comparisons ◽

Nontranslated Region ◽

The Family ◽

Complete Sequences

ABSTRACT The species Human enterovirus B (HEV-B) in the family Picornaviridae consists of coxsackievirus A9; coxsackieviruses B1 to B6; echoviruses 1 to 7, 9, 11 to 21, 24 to 27, and 29 to 33; and enteroviruses 69 and 73. We have determined complete genome sequences for the remaining 22 HEV-B serotypes whose sequences were not represented in public databases and analyzed these in conjunction with previously available complete sequences in GenBank. Members of HEV-B were monophyletic relative to all other human enterovirus species in all regions of the genome except in the 5′-nontranslated region (NTR), where they are known to cluster with members of HEV-A. Within HEV-B, phylogenies constructed from the structural (P1) and nonstructural regions of the genome (P2 and P3) are incongruent, suggesting that recombination had occurred. Similarity plots and bootscanning analysis across the complete genome identified multiple sites at which the phylogeny of a given strain's sequence shifted, indicating potential recombination points. These points are distributed in the 5′-NTR and throughout P2 and P3, but no sites with >80% bootstrap support were identified within the capsid. Individual sequence comparisons and phylogenetic analyses suggest that members of HEV-B have recombined with one another on multiple occasions, resulting in a complex mosaic of sequences derived from multiple parental viruses in the nonstructural regions of the genome. We conclude that RNA recombination is a common mechanism for enterovirus evolution and that recombination within the nonstructural regions of the genome (P2 and P3) has been observed only among members of the same species.

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Molecular Phylogeny and Proposed Classification of the Simian Picornaviruses

Journal of Virology ◽

10.1128/jvi.76.3.1244-1251.2002 ◽

2002 ◽

Vol 76 (3) ◽

pp. 1244-1251 ◽

Cited By ~ 56

Author(s):

M. Steven Oberste ◽

Kaija Maher ◽

Mark A. Pallansch

Keyword(s):

Enterovirus 71 ◽

Amino Acid Identity ◽

Simian Virus ◽

Human Enterovirus ◽

Culture Methods ◽

True Number ◽

Coxsackievirus A9 ◽

Coxsackie B Viruses ◽

Coxsackie B

ABSTRACT The simian picornaviruses were isolated from various primate tissues during the development of general tissue culture methods in the 1950s to 1970s or from specimens derived from primates used in biomedical research. Twenty simian picornavirus serotypes are recognized, and all are presently classified within the Enterovirus genus. To determine the phylogenetic relationships among all of the simian picornaviruses and to evaluate their classification, we have determined complete VP1 sequences for 19 of the 20 serotypes. Phylogenetic analysis showed that A13, SV19, SV26, SV35, SV43, and SV46 are members of human enterovirus species A, a group that contains enterovirus 71 and 11 of the coxsackie A viruses. SA5 is a member of human enterovirus species B, which contains the echoviruses, coxsackie B viruses, coxsackievirus A9, and enterovirus 69. SV6, N125, and N203 are related to one another and, more distantly, to species A human enteroviruses, but could not be definitely assigned to a species. SV4 and SV28 are closely related to one another and to A-2 plaque virus, but distinct from other enteroviruses, suggesting that these simian viruses are members of a new enterovirus species. SV2, SV16, SV18, SV42, SV44, SV45, and SV49 are related to one another but distinct from viruses in all other picornavirus genera, suggesting that they may comprise a previously unknown genus in Picornaviridae. Several simian virus VP1 sequences (N125 and N203; SV4 and SV28; SV19, SV26, and SV35; SV18 and SV44; SV16, SV42, and SV45) are greater than 75% identical to one another (and/or greater than 85% amino acid identity), suggesting that the true number of distinct serotypes among the viruses surveyed is less than 20.

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