Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen for the global pork industry. Modified live virus (MLV) vaccines are widely used for PRRSV prevention and control. However, MLV vaccines can still infect hosts and replicate in the target cells, increasing the risk of virus recombination and reversion to virulence. Recently, a highly pathogenic PRRSV strain appeared in December 2024, causing severe outbreaks on a PRRSV-negative pig farm in Yunnan, China. The isolated strain exhibited 99.4%-99.5% nucleotide similarity to the historical JXA1-R vaccine-derived revertant isolated in 2012, despite the farm never using JXA1-R vaccines. Ten unique amino acid mutations confirmed that this strain was a revertant derived from JXA1-R vaccines, which reverted to cause an outbreak in 2012 and vanished for 12 years.IMPORTANCECurrently, there is a relative consensus that porcine reproductive and respiratory syndrome modified live virus (PRRS MLV) has the highest protective efficacy against the genetically homologous virus, compared with commercially available killed vaccines or other kinds of vaccines under development. However, risks of virulence reversion remain in such live vaccines. This case reveals the unpredictable risks of live-attenuated vaccines. The findings underscore the inherent flaws in highly pathogenic PRRSV MLV vaccines, emphasizing the need for safer vaccine designs. The re-emergence of that revertant draws our attention to its source, and the similar mutation site compared with 12 years ago could indicate key nucleotide sites for the reversion of virulence of this strain.