Submitted to: Virus Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 3, 2001
Publication Date: November 5, 2001
Interpretive Summary: Infection with bovine viral diarrhea viruses (BVDV) are a source of major economic loss to U.S. cattle producers. Efforts to detect and prevent BVDV infection are hampered by the tendency of BVDV to constantly change or mutate. One of the ways BVDV mutate is to pick up pieces of genetic material from the cell they have infected and incorporate this material into their own genes. Incorporation of cell genetic material can affect the way the virus behaves. In this study we isolated the cellular gene that donates the genetic material that causes the switch from a virus that doesn't kill cells to a virus that kills cells. We found that the protein from this gene was produced in all cells. Further, we found that more of this protein was made following infection with BVDV, possibly because of stress on the cell. This information will help in understanding how and why BVDV mutate. Understanding how and why BVDV mutate will help in designing BVDV vaccine strains that are stable and do not mutate.
Technical Abstract: Bovine viral diarrhea viruses (BVDV) exist as two biotypes, cytopathic and noncytopathic, based on their ability to produce cytopathology in cultured cells. 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 resulting in 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.