The nonstructural protein 2 (nsp2)-encoding region is one of the most variable regions in PRRSV genome,with various deletions (insertions) have been reported.However,the molecular mechanism which drives such hypervariability is still unknown.In this study,we characterized a cell-culture attenuated type 2 PRRSV isolate,NA 04-30.The virus was continuously passaged 80 times in MARC-145 cells.Full-length genome sequence analysis showed that NA 04-30 virus shares 98.4％ nucleotide identity with VR-2332,the prototypic North American type 2 strain.In comparison to the P1 virus,the NA 04-30 P80 contains a large 123 amino acid (aa) deletion (nucleotide 3221 to 3593 of the viral genome) in the central region of nsp2.Most importantly,this 123 aa deletion region overlaps with a 144 aa deletion region recently reported in a Chinese field isolate,NJ1106 (Du et al.,2012,JVI,86:13883-13884);and in vivo characterization in a nursery pig model demonstrated that the N J-1106 was less virulent in comparison to HP-PRRSV strain JXA1.In our study,a swine cytokine assay showed that NA 04-30 P80 was able to induce higher level of interferon response in virus-infected swine alveolar macrophages,compared to that of NA04-30 P1,VR2332 and other typical PRRSV isolates.Sequence analysis showed that both 123 aa and 144 aa deletion regions contain predicted T-cell and B-cell epitopes.Results from this study suggested that N J1106 might be initially derived from a cell-culture attenuated virus,and the unique deletion (123/144 aa) in nsp2 could contribute to the attenuation of viral pathogenesis.The selective pressure of the host immune system could be one of the driving forces for adaptation of the virus in the new environment,resulting in deletions (insertions) in the nsp2 region.