Lumpy Skin Disease (LSD) is a viral disease that predominantly affects cattle. First identified in an outbreak in Zambia in 1929, the disease is caused by the LSD virus (LSDV), a poxvirus of the genus capripoxvirus. Until the 1980s. multiple outbreaks of LSD were confined to the African continent. The first reports of infections outside Africa were in 1989 from Israel. In 2016, LSD was reported from Russia and South-East European nations. In the Indian subcontinent, the disease was initially observed in Bangladesh in 2019, followed by China, India, Nepal, Bhutan, Vietnam, Hong Kong and Myanmar.
The first complete genome sequence of LSDV (Neethling strain) was available in 2001 and suggested a large DNA genome. This strain was originally isolated in Kenya in 1958. Adaptation of poxviruses are dominated by genomic mutations, deletions and recombinations. Subsequent genomes from major outbreaks have provided quite interesting insights into the virus and its evolution.
Recombinant viruses
LSD outbreaks were reported in Russia during 2015-2019. The virus isolated from 2015 and 2016 was similar to the earlier genomes. However, the use of homologous (attenuated) LSDV vaccine in 2016 did not end the outbreak and subsequently vaccine-like isolates were obtained from affected cattle in 2017. By 2018, all field isolates of LSDV in Russia were replaced by viruses bearing genetic signatures of the LSDV vaccine, suggesting that the outbreak of LSD in Russia during 2017-2019 was due to a novel LSDV recombinant variant.
LSDV infections in China were first reported following outbreaks in several regions in 2019. Whole-genome sequencing revealed another vaccine-recombinant strain with 25 recombination events between a field strain and a vaccine strain. However, the strain from China was distinctly different from the vaccine-recombinants detected from Russia, implying that a virulent recombinant of LSDV with unknown origin was the cause of LSD outbreaks in China in 2019 and subsequently in 2020.
Recombination events are now well catalogued in poxviruses and mediated by the poxvirus DNA polymerases in cells being co-infected by viruses of same or different genus. Recombination of pathogenic and vaccine strains are, therefore, likely when an infected animal is immunised or infection occurs in the pre-immune phase after vaccination. Utmost caution and followup genomic studies are therefore essential before full rollout of homologous attenuated vaccines.
Genomes from India
In August 2019, suspected cases of LSD were observed in Odisha. The first laboratory-confirmed outbreak of LSD was subsequently reported in November 2019. The overall infection rate was estimated to be 7%, with little mortality. Sequences of particular genes of the isolated virus from the 2019 outbreak were genetically similar to strains from Kenya.
In July 2022, large outbreak of LSD was reported from Gujarat and Rajasthan, which subsequently spread to 11 other States in a short span affecting Punjab, Haryana, Himachal Pradesh, Jammu & Kashmir, Uttarakhand, Uttar Pradesh, Delhi, Madhya Pradesh, Jharkhand, Maharashtra and Andaman & Nicobar with over 80,000 cattle deaths.
In collaboration with the Department of Animal Husbandry in Rajasthan, CSIR-IGIB reported the whole genome sequences of six isolates of LSDV collected from five affected animals. A total of 177 unique mutations were found compared to the Neethling strain from Kenya. Out of these, 47 were not present in any other global genome sequences of LSDV, implying that the mutations are unique to the 2022 outbreak of LSDV infections in India.
Phylogenetic analysis of the isolates showed that the current virus strain is unrelated to the virus found in India as well as other global genomes of LSDV. The closest genomes to the viral isolates from the current outbreak comprise 12 sequences belonging to other Asian and European countries that were collected from 2012-2022. Further, the presence of an additional mutation in two samples from the same animal and the large number of mutations potentially suggests that LSDV may be able to evolve fast within the host.
Genome surveillance
COVID-19 pandemic underlined the importance of continuous genomic surveillance for evidence-based public health strategies to combat the disease, and development of diagnostic tools and vaccines. Establishing genomic surveillance of transboundary and emerging infectious agents of high consequence is therefore essential for early detection as well as devising evidence based interventions for limiting their spread and minimising economic and strategic losses.
We need to accept that animal and plant health are key to human health and well-being, and forms the basis of One Health. As we move towards industrialised agriculture and animal husbandry in the era of climate change, the need has never been acute for preparedness with newer and better tools like genomics, molecular surveillance and digital technologies to warn, inform, identify and stop emerging pathogens in their tracks.
(The authors are researchers at the CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB), Delhi. Views expressed are personal)
