Evidence A.2 lineage of monkeypox is mutating

In a recently published study bioRxiv* Preprint Server, a team of researchers from India analyzed entire monkeypox virus genome sequences isolated from monkeypox patients with and without an international travel history to understand the phylogenetic relationships and genomic evolution of the virus that could contribute to higher transmission rates.

Study: Genome Characterization of Monkeypox Cases Detected in India: Identification of Three Subclusters Within the A.2 Lineage.  Photo credit: NIAID

Study: Genome Characterization of Monkeypox Cases Detected in India: Identification of Three Subclusters Within the A.2 Lineage. Photo credit: NIAID


The monkeypox virus, like causing smallpox Variola virusis a orthopox virus Species belonging to the Poxviridae Family. It is a double-stranded deoxyribonucleic acid (DNA) virus with a genome that encodes about 190 genes.

The first known human case of monkeypox occurred in 1970 in the Democratic Republic of the Congo, which spread to countries in West and Central Africa, with subsequent outbreaks in the United States (US) in 2003 and the United Kingdom (UK) in 2018. Genome studies conducted by the World Health Organization (WHO) identified two major clades – clade I (Congo Basin clade) and clade II (West Africa clade) with two subclades within clade II. The global monkeypox outbreak in 2022 was associated with clade IIb in connected.

viruses from the Poxviridae families have shown high inter- and intra-species recombination frequencies. Clades I and II had a genetic spacing of 900 bp. The genetic changes could bring transmission and infection advantages to the virus. Therefore, whole genome analyzes of circulating strains of monkeypox virus are essential for disease surveillance.

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About the study

The present study collected samples of nasopharyngeal and oropharyngeal swabs, lesion crusts and fluids from 96 individuals suspected of having monkeypox. The positive cases were identified by real-time polymerase chain reaction (PCR) using monkeypox-specific primers.

The final sample set included five samples from Kerala (with international travel histories) and five from Delhi (without international travel histories). The negative samples were further screened for enterovirus and varicella zoster virus.

Next-generation sequencing was used for the genomic characterization of the positive samples. In addition, phylogenetic analyzes were performed on a final data set consisting of genome sequences generated in this study and 75 sequences from the NCBI (National Center for Biotechnology Information) and GISAID (Global Initiative on Sharing Avian Influenza Data) databases that were previously generated. and monkeypox outbreak after 2022.


In the study, 90% to 99% of the monkeypox genome was recovered from the lesion crust and fluid samples from all positive cases. The phylogenetic trees placed the 10 specimens from India in clade IIb lineage A.2, along with eight other specimens from the US, Thailand and the UK

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The genome-based analysis divided the A.2 lineage into three subclusters with seven sequences (five from Kerala and two from Delhi) branching off with strains UK-2022 OP331335.1 and USA-2022 ON674051.1 forming one subcluster. Lineage-defining mutations at positions C 179537 T, C 25072 T, and A 140492 C further classified the five sequences from Kerala as sublineage A.2.1.

The remaining three sequences from Delhi branched with USA-2022 strain ON675438.1 and formed the second subcluster. The third subcluster consisted of sequences from other US and UK strains and samples from Thailand.

Studies have linked the short-term evolution of monkeypox virus to mutations in the apolipoprotein B editing complex (APOBEC3) genes that result in cytidine deaminase activity. The genome analysis of the present study revealed 13 new APOBEC3 mutations and 16 single nucleotide polymorphisms (SNPs), which the authors believe are lineage-defining changes within the A.2 lineage. The study also identified 25 additional APOBEC3 mutations in the monkeypox strains circulating in India.

The monkeypox sequences from India differed from previous lineages such as B.1 from European countries such as Germany, Italy and France and the 2017-2018 A.1 lineage from Nigeria, Singapore and Israel.


In summary, the study reports 13 novel mutations in the monkeypox virus APOBEC3 gene that may be involved in the evolution of the virus. In addition, the results also uncovered 16 new SNPs that, along with the APOBEC3 mutations, caused samples from India to form lineage A.2.1. The authors believe that mutations in the orthopox virus Genes are associated with increased virulence through immunosuppression in the host.

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Furthermore, genes in the terminal region of monkeypox virus and others orthopox virus Species are responsible for host adaptation and transmission. Therefore, genome-wide studies to understand the role of these genes and to monitor emerging mutations are essential to contain the spread of monkeypox.

*Important NOTE

bioRxiv publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health behavior or treated as established information.

Magazine reference:

  • Genome Characterization of Monkeypox Cases Detected in India: Identification of Three Subclusters in the A.2 Lineage: Anita M. Shete, Pragya D. Yadav, Abhinendra Kumar, Savita Patil, Deepak Y. Patil, Yash Joshi, Triparna Majumdar, Vineet Relhan, Rima R Sahay, Meenakshy Vasu, Pranita Gawande, Ajay Verma, Arbind Kumar, Shivram Dhakad, Anukumar Bala Krishnan, Shubin Chenayil, Suresh Kumar and Priya Abraham. bioRxiv. 2022. DOI: https://doi.org/10.1101/2022.09.16.507742, https://www.biorxiv.org/content/10.1101/2022.09.16.507742v1

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