Identification of a novel Indian clade of Coxsackievirus A16 in Hand, Foot and Mouth disease outbreak in 2022

Abstract

Aim: In 2022, there was a severe hand, foot and mouth disease (HFMD) outbreak in India. This study focuses on the identification and molecular characterization of the causative agent. Methods: 51 suspected HFMD patients were examined. Viral RNA from HFMD-positive patients' vesicular extracts were sequenced. Phylogenetic analysis was carried out for genotype and mutation identification in current outbreak strains. Results: Phylogenetic analysis revealed a novel Indian clade of CVA16 belonging to genotype B1c. Two consistent mutations, R41H in the VP3 protein and G492T in the conserved 5′-UTR region, were found only in novel clade strains. Conclusion: The present study highlights the possibility and significance of the aforementioned mutations in increasing the ability of CVA16 to spread among adults.

Plain language summary

Hand, foot and mouth disease (HFMD) outbreaks are usually caused by a virus called Coxsackievirus A16. This virus mainly affects children under 5 years old. Our study looks at the virus that caused an outbreak of HFMD in India in 2022. This virus was found to have unique mutations its genetic material compared with previously reported strains. These mutations may have made the virus more able to spread and affect an adult population. These mutations should be studied further to develop treatments for future HFMD outbreaks caused by this new strain of Coxsackievirus A16.

Article highlights

• In contrast to previous studies, the current study has a higher number of hand, foot and mouth disease positive cases in the adult population.

• Identification of a novel Indian clade of CVA16 belonging to B1c genotype.

• Two consistent mutations, R41H in the VP3 protein and G492T in the conserved 5′-UTR region, were found only in the novel Indian clade strains and could potentially be involved in the increased transmissibility of the virus in the adult population.

Keywords: :

• 5′-UTR
• CVA16
• HFMD
• India
• mutations
• phylogeny
• VP3

Supplemental material

Supplemental data for this article can be accessed at https://doi.org/10.1080/17460794.2024.2350247

Author contributions

P Mamidi and B Mishra conceived the data, designed the experiments, contributed to data analysis and letter writing. S Panda, M Mohanty, MC Mandal and D Santra contributed to sample collection, preliminary screening of the clinical samples and data analysis. A Ray and E Laha contributed to Sanger sequencing and in cell culture adaptation of the virus for whole genome sequencing. DK, VK Biswas and S Raghav contributed to genome sequencing and data analysis. BR Kar, M Nayak and B Dwibedi contributed to patient diagnosis, and data analysis. B Mishra, S Chattopadhyay and S Raghav contributed to overall supervision of the experiments and data analysis.

Financial disclosure

The corresponding author of this study was supported by the grant number ICMR/AIIMSB/D019/2021/00075, awarded by the Indian Council of Medical Research (ICMR). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The investigations were conducted in accordance with the guidelines set by the IHEC, AIIMS, Bhubaneswar (Ref No: T/IM-NF/Micro/22/22). Written consent was obtained from each patient suspected of having HFMD and permission was obtained for the use of pictures in research publication.

Data availability statement

The CVA16 5′-UTR sequences (Genbank Accession Nos: OR460642-OR460646) and the CVA16 new genome sequence (Genbank Accession No: OR750554) have been submitted to the NCBI Genbank.

Additional information

Funding

The corresponding author of this study was supported by the grant number ICMR/AIIMSB/D019/2021/00075, awarded by the Indian Council of Medical Research (ICMR).