# Biological characteristics of an enterovirus A71 subgroup C4 strain isolated in China

**Authors:** Tianli Ma, Huan Li, Yunfang Li, Weishi Lin, Zhengying Yu, Lizhong Li, Wei Zhang, Hongbin Song, Leili Jia, Jing Xie

PMC · DOI: 10.1186/s12879-025-12241-2 · BMC Infectious Diseases · 2025-12-04

## TL;DR

This study analyzes a Chinese EV-A71 C4 strain, revealing its strong infectivity and impact on cell function and the blood-brain barrier.

## Contribution

The study provides new insights into the biological behavior of a Chinese EV-A71 C4 strain and its effects on host cells.

## Key findings

- GD10 caused significant cytopathic effects and increased viral RNA in RD cells but not in Vero cells.
- GD10 compromised blood-brain barrier integrity and crossed it in vitro.
- The strain showed strong adaptability to RD cells and reduced cell viability through increased LDH and decreased ATP.

## Abstract

Hand, foot, and mouth disease (HFMD) is a widespread infectious disease primarily affecting infants and young children. Enterovirus A71 (EV-A71) comprises eight genogroups, among which subgroup C4 is the dominant viral agent in China and is frequently associated with HFMD and central nervous system infections. The genetic characteristics of an EV-A71 subgroup C4 strain obtained in this study were analyzed using whole-genome sequencing. Its biological characteristics, including infectivity, replication, and cytotoxicity, were investigated in human rhabdomyosarcoma (RD) and African green monkey kidney (Vero) cells.

A clinical EV-A71 C4 subgourp GD10 strain isolated in China was examined to evaluate its genetic and biological features. Its relationships with strains listed in GenBank were evaluated using phylogenetic analysis. Viral infectivity and replication were assessed in RD and Vero cells. Cytotoxicity was evaluated by measuring cell viability, lactate dehydrogenase (LDH) release, and ATP levels. Effects on blood–brain barrier (BBB) integrity were investigated in vitro by assessing transendothelial electrical resistance and viral load across the barrier.

Sequence analysis confirmed that GD10 belonged to subgroup C4 and closely resembled strains from China. GD10 infection induced a pronounced cytopathic effect and elevated viral RNA levels in RD cells but not in Vero cells. The infection time-dependently increased LDH release and reduced ATP levels. GD10 compromised BBB integrity and crossed the cellular barrier in vitro.

The GD10 strain demonstrated strong adaptability to RD cells and impaired BBB function. Our results improve the understanding of virus–host interactions and may support efforts towards EV-A71 vaccine development.

Not applicable

The online version contains supplementary material available at 10.1186/s12879-025-12241-2.

## Linked entities

- **Diseases:** Hand, foot, and mouth disease (MONDO:0005779)
- **Species:** Homo sapiens (taxon 9606), Mus musculus (taxon 10090)

## Full-text entities

- **Diseases:** infection (MESH:D007239), infectious disease (MESH:D003141), HFMD (MESH:D006232), RD (MESH:D012208), Cytotoxicity (MESH:D064420), central nervous system infections (MESH:D002494)
- **Chemicals:** ATP (MESH:D000255)
- **Species:** Homo sapiens (human, species) [taxon 9606], Enterovirus A71 (no rank) [taxon 39054]
- **Cell lines:** Vero — Chlorocebus sabaeus (Green monkey), Spontaneously immortalized cell line (CVCL_0059), RD — Homo sapiens (Human), Embryonal rhabdomyosarcoma, Cancer cell line (CVCL_JB74), African green monkey kidney — Chlorocebus aethiops (Green monkey), Embryonic stem cell (CVCL_RY74)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12781644/full.md

## References

7 references — full list in the complete paper: https://tomesphere.com/paper/PMC12781644/full.md

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Source: https://tomesphere.com/paper/PMC12781644