Two distinct virulent variants of the Lumpy Skin Disease Virus (LSDV) were responsible for the catastrophic outbreak of lumpy skin disease that swept among the livestock in India, claiming approximately 1,00,000 cows across the country in 2022, scientists from the Bengaluru-based Indian Institute of Science (IISc) have revealed in a study.

The outbreak had severely affected India’s agricultural sector, leading to staggering economic losses. “It was a calamity in some ways … a national emergency,” said Utpal Tatu, Professor in the Department of Biochemistry, Indian Institute of Science (IISc) who was part of the multi-institutional team that decided to probe the cause of the outbreak.

These variants, characterized by a high number of genetic variations, are associated with increased disease severity, said the study, underscoring the critical role of genomic analysis in understanding and combating emerging infectious diseases affecting livestock.

The study is published in BMC Genomics. A viral infection caused by the Lumpy Skin Disease Virus (LSDV), the disease is transmitted by insects like flies and mosquitoes. It causes fever and skin nodules, and can be fatal for cattle.  There have been two major outbreaks of this disease in India, the first in 2019 and a more severe outbreak in 2022, infecting more than two million cows.

To investigate the current outbreak, the team collected skin nodules, blood and nasal swabs from infected cattle in various states, including Gujarat, Maharashtra, Rajasthan and Karnataka, in collaboration with veterinary institutes. They performed advanced whole-genome sequencing of DNA extracted from 22 samples.

“The biggest challenge was the lack of an established LSDV genome sequencing and analysis pipeline. We had to adapt techniques from COVID-19 research,” explained Ankeet Kumar, from IISc and co-lead author. “Data was also limited, so we compiled all available global LSDV genome sequences to make our analysis robust.”

The genomic analysis revealed two distinct LSDV variants circulating in India, one with a low number of genetic variations and another with a high number of variations, similar to strains from a 2015 Russian outbreak. Kumar noted the surprising finding of highly varied LSDV strains in India, given the generally stable nature of DNA viruses like LSDV. The team identified over 1,800 genetic variations, including deletions, insertions, and single-letter changes in DNA. The samples with high variations, however, turned out to be similar to LSDV strains from an outbreak in Russia in 2015.

Kumar said that there are no previous reports of such highly varied LSDV strains in India. Viruses that have DNA as the genetic material - like LSDV — are generally more stable than RNA viruses. Therefore, finding so many genetic variations was quite surprising, and could explain the severity of the disease, he added. The variation was as high as 1,800.

Importantly, the scientists also found a large number of genetic variations in viral genes critical for binding to host cells, evading immune response, and replicating efficiently. This likely enhanced the virus’s ability to cause disease. “Cattle developed more severe symptoms in areas where we found highly diverse strains. This suggests that the genetic variations could elevate virulence,” warned Kumar.