Evidence of Recombination among Enteroviruses

Santti, Juhana; Hyypiä, Timo; Kinnunen, Leena; Salminen, Mika

doi:10.1128/jvi.73.10.8741-8749.1999

Cited by 217 publications

(105 citation statements)

References 41 publications

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“…Recombination is a well-known phenomenon in enterovirus evolution. Our present findings are in line with a previous study demonstrating that several recombination breakpoints were located within the P2 and P3 regions of enteroviruses of same species, while no breakpoint was found within the P1 region by genomic analysis [30]. Other studies have also shown recombination sites located within non-structural regions, such as 2A in EV11/EV19 [24], 2B in coxsackievirus B4 [22], and 2C in echovirus 9/18 [2].…”

Section: Discussionsupporting

confidence: 92%

Emergence of enterovirus 71 “double-recombinant” strains belonging to a novel genotype D originating from southern China: first evidence for combination of intratypic and intertypic recombination events in EV71

Yip

Lau

Zhou³

et al. 2010

Arch Virol

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Hand-foot-mouth disease due to enterovirus 71 (EV71) and coxsackievirus A16 (CA16) has recently caused large outbreaks in mainland China in 2008. We performed complete genome sequencing on two EV71 (SZ/HK08-5 and SZ/HK08-6) and two CA16 (SZ/HK08-3 and SZ/HK08-7) strains from patients in Shenzhen, China. Phylogenetic, similarity plot and bootscan analyses revealed recombination between EV71 genotypes B and C at the 2A-2B junction, and between EV71 genotype B and CA16 strain G-10 in the 3C region for EV71 strains. A similar phenomenon was also found upon further gene sequencing with other EV71 strains. Recombination between CA16 strain G-10 and EV71 genotype A at the 2A-2B junction was also observed for CA16 strains. The present "double-recombinant" EV71 strains circulating in China and other EV71 subgenotype "C4" strains represent an additional genotype, D. CA16 strains should also be classified into two genotypes. This represents the first evidence for a combination of intratypic and intertypic recombination in EV71 strains.

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Section: Discussionsupporting

confidence: 92%

Emergence of enterovirus 71 “double-recombinant” strains belonging to a novel genotype D originating from southern China: first evidence for combination of intratypic and intertypic recombination events in EV71

Yip

Lau

Zhou³

et al. 2010

Arch Virol

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“…Taken together, our results suggest that in contrast to the 5=UTR, which displays a high interchangeability potential, the RV recombination possibilities at the polyprotein coding region level are more limited and viable only if involving two members of the same type or of the same species. These global findings are consistent with observations obtained from circulating RV and non-RV EV recombinants (20)(21)(22)27).…”

Section: Discussionsupporting

confidence: 91%

“…Recombination has been extensively described as an evolutionary force for both polio-and non-polio-enteroviruses (EVs) (20)(21)(22). This phenomenon is relatively rare and is mostly related to ancient events among RVs.…”

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confidence: 99%

Chimeric Rhinoviruses Obtained via Genetic Engineering or Artificially Induced Recombination Are Viable Only if the Polyprotein Coding Sequence Derives from the Same Species

Schibler

Piuz

Hao³

et al. 2015

J Virol

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Recombination is a widespread phenomenon that ensures both the stability and variation of RNA viruses. This phenomenon occurs with different frequencies within species of the Enterovirus genus. Intraspecies recombination is described frequently among non-rhinovirus enteroviruses but appears to be sporadic in rhinoviruses. Interspecies recombination is even rarer for rhinoviruses and mostly is related to ancient events which contributed to the speciation of these viruses. We reported that artificially engineered 5= untranslated region (UTR) interspecies rhinovirus/rhinovirus or rhinovirus/non-rhinovirus enterovirus recombinants are fully viable. Using a similar approach, we demonstrated in this study that exchanges of the P1-2A polyprotein region between members of the same rhinovirus species, but not between members of different species, give rise to competent chimeras. To further assess the rhinovirus intra-and interspecies recombination potential, we used artificially induced recombination by cotransfection of 5=-end-deleted and 3=-end-deleted and replication-deficient genomes. In this system, intraspecies recombination also resulted in viable viruses with high frequency, whereas no interspecies rhinovirus recombinants could be recovered. Mapping intraspecies recombination sites within the polyprotein highlighted recombinant hotspots in nonstructural genes and at gene boundaries. Notably, all recombinants occurring at gene junctions presented in-frame sequence duplications, whereas most intragenic recombinants were homologous. Taken together, our results suggest that only intraspecies recombination gives rise to viable rhinovirus chimeras in the polyprotein coding region and that recombination hotspots map to nonstructural genes with in-frame duplications at gene boundaries. These data provide new insights regarding the mechanism and limitations of rhinovirus recombination. IMPORTANCERecombination represents a means to ensure both the stability and the variation of RNA viruses. While intraspecies recombination is described frequently among non-rhinovirus enteroviruses, it seems to occur more rarely in rhinoviruses. Interspecies recombination is even rarer in this virus group and is mostly related to ancient events, which contributed to its speciation. We used engineered chimeric genomes and artificially induced RNA recombination to study experimentally the recombination potential of rhinoviruses and analyze recombination sites. Our results suggest that only intraspecies recombination gives rise to viable chimeras in the polyprotein coding region. Furthermore, characterization of intraspecies chimeras provides new insight into putative recombination hotspots within the polyprotein. In summary, we applied two powerful and complementary experimental approaches to improve current knowledge on rhinovirus recombination. R hinoviruses (RVs) are small positive-stranded RNA viruses belonging to the Enterovirus genus within the Picornaviridae family (http://www.picornaviridae.com/enterovirus/enterovirus .htm) an...

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“…In this study, genetic recombination event were found between the Fuyang HEV71 isolates, including both fatal cases and non-fatal cases, and CV-A16, which was similar to other studies [18,19]. For enteroviruses [20] and dengue viruses [21], genetic recombination is a well-known phe-nomenon and recombination could result in the emergence of viruses with altered pathogenic potentials. Except for the Fuyang HEV71 isolates, genetic recombination was also found in the HEV71 viruses, circulated in mainland of China during 1998-2008.…”

Section: Discussionsupporting

confidence: 88%

An emerging recombinant human enterovirus 71 responsible for the 2008 outbreak of Hand Foot and Mouth Disease in Fuyang city of China

Yan

Zhu

Yang

et al. 2010

Virol J

425

372

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Hand, foot and mouth disease (HFMD), a common contagious disease that usually affects children, is normally mild but can have life-threatening manifestations. It can be caused by enteroviruses, particularly Coxsackieviruses and human enterovirus 71 (HEV71) with highly variable clinical manifestations. In the spring of 2008, a large, unprecedented HFMD outbreak in Fuyang city of Anhui province in the central part of southeastern China resulted in a high aggregation of fatal cases. In this study, epidemiologic and clinical investigations, laboratory testing, and genetic analyses were performed to identify the causal pathogen of the outbreak. Of the 6,049 cases reported between 1 March and 9 May of 2008, 3023 (50%) were hospitalized, 353 (5.8%) were severe and 22 (0.36%) were fatal. HEV71 was confirmed as the etiological pathogen of the outbreak. Phylogenetic analyses of entire VP1 capsid protein sequence of 45 Fuyang HEV71 isolates showed that they belong to C4a cluster of the C4 subgenotype. In addition, genetic recombinations were found in the 3D region (RNA-dependent RNA polymerase, a major component of the viral replication complex of the genome) between the Fuyang HEV71 strain and Coxsackievirus A16 (CV-A16), resulting in a recombination virus. In conclusion, an emerging recombinant HEV71 was responsible for the HFMD outbreak in Fuyang City of China, 2008.

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Evidence of Recombination among Enteroviruses

Cited by 217 publications

References 41 publications

Emergence of enterovirus 71 “double-recombinant” strains belonging to a novel genotype D originating from southern China: first evidence for combination of intratypic and intertypic recombination events in EV71

Emergence of enterovirus 71 “double-recombinant” strains belonging to a novel genotype D originating from southern China: first evidence for combination of intratypic and intertypic recombination events in EV71

Chimeric Rhinoviruses Obtained via Genetic Engineering or Artificially Induced Recombination Are Viable Only if the Polyprotein Coding Sequence Derives from the Same Species

An emerging recombinant human enterovirus 71 responsible for the 2008 outbreak of Hand Foot and Mouth Disease in Fuyang city of China

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