Propagation and immunological characterization of coxsackievirus A10 in a serum-free HEK293A cell culture system

Lien, Sheng-Chieh; Shen, Yu-Sheng; Lin, Hsiu-Li; Wu, Shang Yin; Fang, Chih‐Yeu; Chen, Chi-Hsun; Chen, Yi‐An; Chong, Pele; Huang, Mao-Hsiung; Chow, Yen‐Hung; Wang, Jen Ren; Wu, Suh-Chin; Liu, Chia-Chyi

doi:10.1016/j.virusres.2023.199101

Cited by 2 publications

(1 citation statement)

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“…A limitation of our study is that due to time and resource constraints, we only used RD cells for CVA10 research and did not investigate the infectivity of wildtype and mutant CVA10 viruses in other enterovirus-sensitive cell lines. Previous studies report that CVA10 can exhibit quite different growth kinetics when infecting different human cell lines, such as RD (rhabdomyosarcoma cells), Hela (cervical epithelial cells), HEK 293A (embryonic kidney cells), KB (oral carcinoma cells), SK-N-SH (neuroblastoma cells), and MRC-5 (lung fibroblasts) [ 33 , 34 ]. This phenomenon is probably due to differences in cell surface expression level of the KRM1 receptor.…”

Section: Discussionmentioning

confidence: 99%

VP2 residue N142 of coxsackievirus A10 is critical for the interaction with KREMEN1 receptor and neutralizing antibodies and the pathogenicity in mice

Li,

Liu,

Yan

et al. 2023

PLoS Pathog

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Coxsackievirus A10 (CVA10) has recently emerged as one of the major causative agents of hand, foot, and mouth disease. CVA10 may also cause a variety of complications. No approved vaccine or drug is currently available for CVA10. The residues of CVA10 critical for viral attachment, infectivity and in vivo pathogenicity have not been identified by experiment. Here, we report the identification of CVA10 residues important for binding to cellular receptor KREMEN1. We identified VP2 N142 as a key receptor-binding residue by screening of CVA10 mutants resistant to neutralization by soluble KREMEN1 protein. The receptor-binding residue N142 is exposed on the canyon rim but highly conserved in all naturally occurring CVA10 strains, which provides a counterexample to the canyon hypothesis. Residue N142 when mutated drastically reduced receptor-binding activity, resulting in decreased viral attachment and infection in cell culture. More importantly, residue N142 when mutated reduced viral replication in limb muscle and spinal cord of infected mice, leading to lower mortality and less severe clinical symptoms. Additionally, residue N142 when mutated could decrease viral binding affinity to anti-CVA10 polyclonal antibodies and a neutralizing monoclonal antibody and render CVA10 resistant to neutralization by the anti-CVA10 antibodies. Overall, our study highlights the essential role of VP2 residue N142 of CVA10 in the interactions with KREMEN1 receptor and neutralizing antibodies and viral virulence in mice, facilitating the understanding of the molecular mechanisms of CVA10 infection and immunity. Our study also provides important information for rational development of antibody-based treatment and vaccines against CVA10 infection.

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Section: Discussionmentioning

confidence: 99%