Natural syndemic infection between African swine fever virus (ASFV) and porcine reproductive and respiratory syndrome virus (PRRSV) leads to shifting of ASFV tissue tropism to lungs with exacerbated presentation of the disease

African swine fever (ASF) and porcine reproductive and respiratory syndrome (PRRS) are two of the most devastating and economically important transboundary diseases of pig. The current epidemic-to-pandemic situation of ASF and the unavailability of broadly effective vaccine against PRRS raise the possibility of these highly pathogenic viruses circulating simultaneously in the same pig population. This study is reporting natural occurrence of syndemic infections of ASF and PRRS in pig population of Mizoram, India. The syndemic infections resulted in high mortality in the affected crossbred pigs, while the indigenous Zovawk pigs revealed some degree of tolerance. The symbiosis between the two viruses resulted in extensive tissue damage in wider range of body systems with multiple organ failure leading to more severe acute disease. The absolute quantification of both the viruses in various organs revealed distinct tissue tropism and suggested shifting of ASFV tissue tropism towards lungs tissues in the naturally occurring syndemic infection of PRRSV and ASFV. The phylogenetic analysis based on the B646L gene of ASFV and the ORF7 gene of PRRSV identified the circulating strains in genotype II ASFV and lineage 8 of PRRSV 2. Our findings underscore the complexity of co-infections in natural cases and emphasize the importance of integrated diagnostics and targeted disease management strategies for the swine population to combat this emerging situation . Highlights • Natural syndemic infections of ASFV and PRRSV were confirmed in pig farms in Mizoram, India, with high mortality in crossbred pigs but partial tolerance in indigenous Zovawk pigs. • Absolute quantification of viral loads revealed distinct organ-specific viral dynamics between ASFV and PRRSV, with ASFV dominating in lungs, liver, and heart, while PRRSV replicated more in kidney, spleen, and lymphoid tissues. • ASFV exhibited a shift in tissue tropism , with the lungs identified as the primary site of highest viral replication. • Syndemic infection involving ASFV and PRRSV caused exacerbated systemic pathology . • Phylogenetic analysis identified ASFV isolates as genotype II and PRRSV isolates as HP-PRRSV lineage 8, showing close relatedness to contemporary Asian strains.