Lumpy skin disease (LSD) has emerged as a global threat to cattle health and production. Although India has been encountering regular episodes of LSD epidemics on the mainland since 2019, the Andaman and Nicobar Islands remained free of LSD until 2021. In this study, we investigated the first LSD outbreak on Great Nicobar Island in 2022 and examined the genetic characteristics of the LSDV strain associated with this outbreak. The morbidity and mortality rates in cattle were 38.29% and 1.89%, respectively. We screened 123 samples (whole blood, nasal swab, or skin tissue) from 111 cattle by LSDV real-time PCR and sera from 86 cattle by LSDV antibody ELISA, and the results confirmed LSDV infection. Subsequent nucleotide sequencing and phylogenetic analysis of five selected marker genes (GPCR, RPO30, P32, EEV, and B22R) revealed that the LSDV strain from Great Nicobar Island resembled cluster 2.5 LSDV recombinant strains from East and Southeast Asia but was distinct from wild-type LSDV strains (1.2.1, 1.2.2) circulating in mainland India, indicating an exotic source of introduction. Phylogenetic analysis using a concatenated sequence (GPCR-RPO30-P32-EEV-B22R) showed that both the wild-type and recombinant LSDV strains formed well-supported clusters, indicating that this type of analysis may be used as an alternative to whole-genome sequence analysis. We also found that determination of the nucleotide sequence of the C-terminal 717 bp of the B22R gene may be sufficient for reliable assignment of circulating LSDV isolates to a particular cluster. This is the first report of the detection of a recombinant LSDV strain in India, demonstrating the spread of cluster 2.5 recombinant LSDV further into South Asia. Our findings highlight the value of LSDV surveillance and genetic analysis for LSDV epidemiology, which may be helpful for developing effective control strategies.

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