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Complete genome sequencing and analysis of six enterovirus 71 strains with different clinical phenotypes

Hong-ling Wen1, Lu-ying Si1, Xiao-jing Yuan1, Shu-bin Hao2, Feng Gao3, Fu-lu Chu1, Cheng-xi Sun1 and Zhi-yu Wang1*

Author Affiliations

1 The Key Laboratory of experimental teratology of Ministry of Education, Department of Virology, School of Public Health, Shandong University, Jinan, Shandong, 250012, People’s Republic of China

2 Shandong Medical Equipment Quality Supervision And Inspection Center, Jinan, Shandong, 250012, People’s Republic of China

3 Linyi People's Hospital, Linyi, Shandong, 276000, People’s Republic of China

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Virology Journal 2013, 10:115  doi:10.1186/1743-422X-10-115

Published: 11 April 2013

Abstract

Background

Hand, foot and mouth diseases (HFMD) caused by enterovirus 71(EV71) presents a broad spectrum of clinical manifestations ranging from mild febrile disease to fatal neurolocal disease. However, the mechanism of virulence is unknown.

Methods

We isolated 6 strains of EV71 from HFMD patients with or without neurological symptoms, and sequenced the whole genomes of the viruses to reveal the virulence factors of EV71.

Results

Phylogenetic tree based on VP1 region showed that all six strains clustered into C4a of C4 sub-genotype. In the complete polypeptide, 298 positions were found to be variable in all strains, and three of these positions (ValP814/IleP814 in VP1, ValP1148/IleP1148 in 3A and Ala P1728/Cys P1728/Val P1728 in 3C) were conserved among the strains with neurovirulence, but variable in strains without neurovirulence. In the 5-UTR region, it showed that the first 10 nucleotides were mostly conserved, however from the 11th nucleotide, nucleotide insertions and deletions were quite common. The secondary structure prediction of 5-UTR sequences showed that two of three strains without neurovirulence (SDLY11 and SDLY48) were almost the same, and all strains with neurovirulence (SDLY96, SDLY107 and SDLY153) were different from each other. SDLY107 (a fatal strain) was found different from other strains on four positions (CP241/TP241, AP571/TP571, CP579/TP579 in 5-UTR and TP7335/CP7335 in 3-UTR).

Conclusions

The three positions (ValP814/IleP814 in VP1, ValP1148/IleP1148 in 3A and Ala P1728/Cys P1728/Val P1728 in 3C), were different between two phenotypes. These suggested that the three positions might be potential virulent positions. And the three varied positions were also found to be conserved in strains with neurovirulence, and variable in strains without neurovirulence. These might reveal that the conservation of two of the three positions or the three together were specific for the strains with neurovirulence. Varation of secondary structure of 5-UTR, might be correlated to the changes of viral virulence. SDLY107 (a fatal strain) was found different from other strains on four positions, these positions might be related with death.

Keywords:
Enterovirus 71; Virulent determinant; Hand, foot and mouth disease