Recombination with a cellular mRNA encoding a novel DnaJ protein results in biotype conversion in genotype 2 bovine viral diarrhea viruses

Bovine viral diarrhea viruses (BVDV) exist as two biotypes, cytopathic and noncytopathic, based on their ability to produce cytopathology in cultured cells. Cytopathic viruses arise from noncytopathic viruses following geneti c alteration (insertions, duplications, rearrangements) within the region e ncoding the NS2/3 protein. In BVDV genotype 2, the majority of biotype conv ersions result from the integration of a cellular mRNA into the genomic RNA of a noncytopathic virus within the NS2/3 coding region. The translation o f the cellular sequences during viral replication results in the proteolyti c cleavage of the nonstructural protein NS2/3 to the NS2 and NS3 proteins w ith the appearance of the cytopathic phenotype. Here, these cellular sequen ces were identified as a portion of a cellular mRNA encoding a novel DnaJ p rotein (bDnaJ1). The 60 amino acid J-domain was identified near the C-termi nus of the protein. Potential nuclear localization, famesylation and hydrop hobic transmembrane domains were also identified. Reverse transcription-PCR analysis of the expression of bDnaJ1 in bovine tissues showed that it was expressed in all tissues examined, and additionally, there may be alternate splicing of the transcript, yielding a second form of the bDnaJ1 protein. Northern blot analysis of mock and BVDV2 infected cells indicated that infe ction by noncytopathic BVDV2 altered the expression level of a bDnaJ1-hybri dizing transcript. The increase in expression may represent a stress respon se to the infection by noncytopathic BVDV. (C) 2001 Elsevier Science B.V. A ll rights reserved.