Why enhancing genomic surveillance is imperative

A recent study revealed that the rate of genetic changes in monkeypox virus was higher than expected

A recent study revealed that the rate of genetic changes in monkeypox virus was higher than expected

Since it was first reported in humans in the 1970’s, monkeypox virus Infection was largely confined to countries in Central and East Africa until recently. In early 2022, multiple cases were identified in Spain and several cases were reported from non-endemic countries, including areas in Europe and North America, and in patients without a history of travel to endemic areas.

After the rapid rise in the number of cases, the World Health Organization (WHO) declared on July 23, 2022, the year 2022 Monkeypox outbreak as a public health emergency International Interests (PHEIC). As of early August 2022, more than 25,000 cases of monkeypox have been reported from 83 countries, 76 of which have historically never reported monkeypox.

watched What is monkeypox virus?

Explainer video about moneypox virus. | Video credit: The Hindu Office

genome sequence

The accelerated use of genomics as a tool for understanding disease outbreaks in the past half-decade has left an indelible mark during the ongoing COVID-19 pandemic and has seen a wider spread of sequencing infrastructure across the globe. Genomic surveillance of pathogens can provide unique insights to better understand outbreaks, track the spread of pathogens, and provide tremendous opportunities for public health decision-making as well as for epidemiology.

Researchers from around the world have made available more than 650 complete genome sequences of monkeypox isolates to date in public domain databases including GISAID and GenBank. This includes more than 600 genomes sequenced this year alone from more than 35 countries, including the genomes of two isolates from India, collected from Kerala.

Read also: Monkeypox virus: origin, symptoms and vaccine

accelerated development

The monkeypox virus has a DNA genome of about 2,00,000 base pairs, nearly six times larger than the SARS-CoV-2 virus. Like other viruses, monkeypox virus develops by accumulating genetic errors, or mutations, in its genome when it replicates within a host. Information about mutations that occur in the different genome sequences of monkeypox virus across different regions can provide key insights into how the virus evolved, its genetic diversity, and other factors that may be relevant to the development of diagnostic tools.

As a DNA virus, monkeypox virus like other smallpox viruses is believed to have a small rate of accumulated genetic changes compared to viruses containing RNA genomes such as SARS-CoV-2, which have a much higher mutation rate. For smallpox viruses, this rate is estimated to be as low as some genetic changes each year. A recent study revealed, however, that it was observed The rate of genetic changes in the virus was higher than expected Average of about 50 genetic changes. The higher-than-expected rate of development combined with the rapid rise in cases of monkeypox worldwide is likely due to a very parallel evolution in a large number of individuals simultaneously, with the current outbreak coming from a super-widespread event.

APOBEC3 . protein

The study also suggests that many of the mutations identified in the new monkeypox virus sequences may have emerged due to the interaction between the virus genome and an important family of proteins encoded by the human genome known as the lipoprotein-editing complex B (or APOBEC3). These proteins provide protection against some types of viral infections by modifying the sequence of the virus’s genome as it replicates in the cell.

Therefore, some researchers suggest that many of the genetic mutations in monkeypox genomes from the current outbreak are remnants of APOBEC3 influence and may not provide a significant evolutionary advantage to the virus.

Monkeypox virus can infect a range of hosts, including non-human primates and rodents that can act as a natural reservoir. Infection in the reservoir can also enable mutations to continue to be transmitted and accumulate before they can spread to cause human infections. Other studies have also suggested an ongoing evolution of the virus, including deletions involving genes as seen in a few genomes from the current outbreak, which may indicate new ways in which the virus continues to evolve with continuous human-to-human transmission.

Monkeypox strains

Groups of genomes with common, common mutations and a common ancestry are referred to as a lineage or clade. In the early 2000s, two different groups of monkeypox virus were identified in Africa where several cases of the disease were seen – the Central African (Congo Basin) and West African clade, which have been shown to be the Congo Basin clade. More transmissible and causes more severe disease.

Since naming viral lineages using country or geography of origin can be discriminatory and perhaps not in the right spirit, researchers have recently proposed a new system for naming monkeypox strains. Under the proposed new system, the clade of the Congo Basin is referred to as clade 1, while the West African clade is subdivided into clade 2 and clade 3. This new system would also describe the sub-lineages of the virus, indicating the original ancestral lineage as “A” lineage and its “A1” lineage. and “A.1.1”, “A2” and “B1”. Lineage B.1 indicates an outbreak of monkeypox virus in 2022 that is descended from the strain A.1.1 strain.

Insights of the 2022 outbreak

With the many genome sequences of monkeypox virus available in public databases, it is possible today to understand the spread of different strains of the virus across different regions. More than 95% of the recently deposited genome sequences of the virus belong to the B.1 strain of monkeypox virus, and this strain is epidemiologically linked to the super-spreading events in Europe that formed the basis for the current monkeypox outbreak.

While the majority of deposited genomes can be linked to the monkeypox outbreak in 2022, sequences deposited recently in 2022 from the United States, Thailand, and India indicate that a second distinct strain of monkeypox virus is currently circulating in 2022. These were classified The genomes are identified as the A.2 strain of monkeypox virus and currently include six genome sequences, including two collected from Kerala. The oldest genome belonging to this strain was collected from Texas in 2021 while the two sequences from Kerala in the 2022 collection were closely collected with a genome collected from Florida in the same year.

Characterization of this distinct lineage amid an outbreak of monkeypox in 2022 suggests that previously undetected transmission of the virus has been occurring in multiple countries, since at least around 2021, and may have been detected due to increased awareness and availability of the disease. of diagnostic tools.

Genetic monitoring of pathogens provides interesting insights through a molecular approach to contact tracing and understanding worldwide transmission of the virus. As the incidence of monkeypox continues to rise, it is therefore important to strengthen genetic surveillance of monkeypox virus. Because data from the current outbreak indicates ongoing human-to-human transmission, ongoing genetic monitoring is important for understanding virus evolution and adaptation, apart from providing useful data for epidemiologists.

With COVID-19 continuing unabated and monkeypox looming, the time has never been better, and the need more urgent, to build a sustainable system of genetic surveillance in India.

( The authors are researchers at the CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB) in Delhi. The opinions expressed are personal)

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