Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jan 12;12(1):593.
doi: 10.1038/s41598-021-04604-x.

A novel subgenotype C6 Enterovirus A71 originating from the recombination between subgenotypes C4 and C2 strains in mainland China

Yongjuan Liu #  1   2   3 , Jingyi Zhou #  4 , Guangquan Ji #  5 , Yupeng Gao  6 , Chunyan Zhang  2   7 , Ting Zhang  1   2 , Juan Huo  1   2 , Wenxue Liang  1   2 , Jin Yang  1   2   7 , Yingying Shi  8 , Shaolin Zhao  9   10   11
Affiliations

A novel subgenotype C6 Enterovirus A71 originating from the recombination between subgenotypes C4 and C2 strains in mainland China

Yongjuan Liu et al. Sci Rep. .

Abstract

Recombination plays important roles in the genetic diversity and evolution of Enterovirus A71 (EV-A71). The phylogenetics of EV-A71 in mainland China found that one strain DL71 formed a new subgenotype C6 with unknown origin. This study investigated the detailed genetic characteristics of the new variant. DL71 formed a distinct cluster within genotype C based on the genome and individual genes (5'UTR, VP4, VP1, 2A, 2B, 2C, 3D, and 3'UTR). The average genetic distances of the genome and individual genes (VP3, 2A, 2B, 2C, 3A, 3C, and 3D) between DL71 and reference strains were greater than 0.1. Nine recombination events involving smaller fragments along DL71 genome were detected. The strains Fuyang-0805a (C4) and Tainan/5746/98 (C2) were identified as the parental strains of DL71. In the non-recombination regions, DL71 had higher identities with Fuyang-0805a than Tainan/5746/98, and located in the cluster with C4 strains. However, in the recombination regions, DL71 had higher identities with Tainan/5746/98 than Fuyang-0805a, and located in the cluster with C2 strains. Thus, DL71 was a novel multiple inter-subgenotype recombinant derived from the dominant subgenotype C4 and the sporadic subgenotype C2 strains. Monitoring the emergence of new variants by the whole-genome sequencing remains essential for preventing disease outbreaks and developing new vaccines.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Phylogenetic tree based on the VP1 sequences of EV-A71. The evolutionary tree was constructed using the maximum likelihood method with the General Time Reversible (GTR) model by MEGAX. Bootstrap values were calculated by 1000 replicates. Bootstrap values lower than 60% are hidden. The branch of subgenotype C4 is compressed to save space. The solid square (black filled square) indicates the new subgenotype C6 EV-A71 strain DL71. CVA16 G-10 was used as the out-group strain. The scale bar indicates the number of nucleotide substitutions per site.
Figure 2
Figure 2
Phylogenetic trees based on the complete genomes and individual genes of DL71 and EV-A71 reference strains. The evolutionary trees based on (a) the complete genomes and individual genes (b) 5′UTR, (c) VP4, (d) VP2, (e) VP3, (f) VP1, (g) 2A, (h) 2B, (i) 2C, (j) 3A, (k) 3B, (l) 3C, (m) 3D and (n) 3′UTR were constructed using the maximum likelihood method with the GTR model by MEGAX. Bootstrap values lower than 60% are hidden. DL71 is labeled with a solid square (black filled square). The asterisk (*) indicates that DL71 is located within the branch of subgenotype C4 in the phylogenetic trees based on (d) VP2, (e) VP3, (j) 3A, (k) 3B, and (l) 3C.
Figure 2
Figure 2
Phylogenetic trees based on the complete genomes and individual genes of DL71 and EV-A71 reference strains. The evolutionary trees based on (a) the complete genomes and individual genes (b) 5′UTR, (c) VP4, (d) VP2, (e) VP3, (f) VP1, (g) 2A, (h) 2B, (i) 2C, (j) 3A, (k) 3B, (l) 3C, (m) 3D and (n) 3′UTR were constructed using the maximum likelihood method with the GTR model by MEGAX. Bootstrap values lower than 60% are hidden. DL71 is labeled with a solid square (black filled square). The asterisk (*) indicates that DL71 is located within the branch of subgenotype C4 in the phylogenetic trees based on (d) VP2, (e) VP3, (j) 3A, (k) 3B, and (l) 3C.
Figure 3
Figure 3
Recombination analyses of DL71. (a) Graphical representation of EV-A71 genome. (b) A schematic map of recombination within DL71 genome. DL71 genome is shown as a red rectangle. The backbone of DL71 is derived from the major parent (green rectangles), while other genetic components of DL71 is derived from the minor parent (brown rectangles). (c) The plot display of 9 recombination events in DL71 genome identified by RDP4. (d) The genome of DL71 was used as the query sequence in the Similarity plot analysis. (e) The genome of DL71 was used as the query sequence in the BootScan analysis. The vertical red line indicates the breakpoint regions.
Figure 4
Figure 4
Phylogenetic trees based on the non-recombination regions of DL71. The regions (a) 1–309 bp, (b) 608–837 bp, (c) 1141–2329 bp, (d) 2701–2948 bp, (e) 3297–3685 bp, (f) 4039–4365 bp, (g) 4668–5813 bp, (h) 6187–6553 bp, and (i) 6915–7215 bp of DL71 and other reference strains were used to construct the phylogenetic trees by the maximum likelihood method with 1000 bootstrap replicates. The recombinant strain DL71 is labeled with a solid square (black filled square), the major parental strain with a solid regular triangle (black filled upward triangle), and the minor parental strain with a solid inverted triangle (black filled downward triangle).
Figure 5
Figure 5
Phylogenetic trees based on the recombination regions of DL71. The regions (a) 310–607 bp, (b) 838–1140 bp, (c) 2330–2700 bp, (d) 2949–3296 bp, (e) 3686–4038 bp, (f) 4366–4667 bp, (g) 5814–6186 bp, (h) 6554–6914 bp, and (i) 7216–7460 bp of DL71 and other reference strains were used to construct the phylogenetic trees by the maximum likelihood method with 1000 bootstrap replicates. The recombinant strain DL71, the major parental strain and the minor parental strain are indicated with “black filled square”, “black filled upward triangle” and “black filled downward triangle”, respectively.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Sun L, et al. Intra-host emergence of an enterovirus A71 variant with enhanced PSGL1 usage and neurovirulence. Emerg. Microbes Infect. 2019;8:1076–1085. - PMC - PubMed
    1. Zhang C, Li Y, Li J. Dysregulated autophagy contributes to the pathogenesis of enterovirus A71 infection. Cell Biosci. 2020;10:142. - PMC - PubMed
    1. Puenpa J, Wanlapakorn N, Vongpunsawad S, Poovorawan Y. The history of enterovirus A71 outbreaks and molecular epidemiology in the Asia-Pacific Region. J. Biomed. Sci. 2019;26:75. - PMC - PubMed
    1. Huang J, et al. Epidemiology of recurrent hand, foot and mouth disease, China, 2008–2015. Emerg. Microbes Infect. 2018;24:432–442. - PMC - PubMed
    1. Chen X, et al. Analysis of recombination and natural selection in human enterovirus 71. Virology. 2010;398:251–261. - PubMed

Publication types

Substances