Genetic variation and pathogenicity of highly virulent porcine reproductive and respiratory syndrome virus emerging in China

A highly pathogenic swine disease designated as 'porcine high fever disease (PHFD)' appeared recently in China. Porcine reproductive and respiratory syndrome virus (PRRSV) was identified as an agent associated with PHFD, and two discontiguous sequence deletions were identified as a genetic marker in the Nsp2 region of the viral genome. To examine PHFD in Shandong province, a total of 10 PRRSV isolates were recovered from pig herds that had never been vaccinated for PRRS. Sequence analysis of open reading frame 5 (ORF5) showed that the level of identity among the 10 isolates ranged between 88.2 and 99.2%. For the non-structural protein 2 (Nsp2) gene, three isolates shared high sequence identity with VR-2332, the prototype virus of the North American genotype, while the remaining seven isolates exhibited two discontiguous sequence deletions that were identical to those of PHFD: a one-amino-acid (phenylalanine) deletion at position 482 and a 29-amino-acid deletion at positions 533-561 of Nsp2. Experimental infection of pigs with SD-JN, which was one of the seven isolates containing such deletions, resulted in severe clinical symptoms characterized by red discoloration on the body and hemorrhages in the lungs, kidneys, and inguinal lymph nodes, accompanied by higher mortality and longer duration of viremia. These symptoms were similar to those of PHFD observed in the field. Our results show that VR2332-like PRRSV coexists with PHFD-associated atypical PRRSV in pig herds in the Shandong area, and different PRRSV isolates differ greatly in their pathogenesis and virulence in pigs.