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 genetic alteration (insertions, duplications, rearrangements) within the region encoding the NS2/3 protein. In BVDV genotype 2, the majority of biotype conversions result from the integration of a cellular mRNA into the genomic RNA of a noncytopathic virus within the NS2/3 coding region. The translation of the cellular sequences during viral replication results in the proteolytic cleavage of the nonstructural protein NS2/3 to the NS2 and NS3 proteins with the appearance of the cytopathic phenotype. Here, these cellular sequences were identified as a portion of a cellular mRNA encoding a novel DnaJ protein (bDnaJ1). The 60 amino acid J-domain was identified near the C-terminus of the protein. Potential nuclear localization, farnesylation and hydrophobic 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 infection by noncytopathic BVDV2 altered the expression level of a bDnaJ1-hybridizing transcript. The increase in expression may represent a stress response to the infection by noncytopathic BVDV.