Effect of the viral protein N(pro) on virulence of bovine viral diarrhea virus and induction of interferon type I in calves.
OBJECTIVE
To characterize the influence of the viral protein N(pro) on virulence of bovine viral diarrhea virus (BVDV) and on type I interferon responses in calves.


METHODS
10 calves, 4 to 6 months of age.


METHODS
BVDV virulence and type I interferon responses of calves (n = 5) infected with a noncytopathic BVDV with a deleted N(pro) were compared with those of calves (5) infected with a noncytopathic BVDV with a functional N(pro). Rectal temperatures, clinical signs, platelet counts, and total and differential WBC counts were evaluted daily. Histologic examinations and immunohistochemical analyses of tissues were conducted to assess lesions and distribution of viral antigens, respectively. Serum type I interferon concentrations were determined.


RESULTS
Calves infected with N(pro)-deleted BVDV developed leukopenia and lymphopenia, without developing increased rectal temperatures or lymphoid depletion of target lymphoid organs. There was minimal antigen deposition in lymphoid organs. Calves infected with N(pro) BVDV developed increased rectal temperatures, leukopenia, lymphopenia, and lymphoid depletion with marked BVDV antigen deposition in lymphatic tissues. Interferon type I responses were detected in both groups of calves.


CONCLUSIONS
Deletion of N(pro) resulted in attenuation of BVDV as evidenced by reduced virulence in calves, compared with BVDV with a functional N(pro). Deletion of N(pro) did not affect induction of type I interferon. The N(pro)-deleted BVDV mutant may represent a safe noncytopathic virus candidate for vaccine development.
Henningson
Jamie N
JN
Department of Veterinary and Biomedical Sciences, College of Agricultural Sciences and Natural Resources, University of Nebraska, Lincoln, NE 68583, USA.
Topliff
Christina L
CL
Gil
Laura H V
LH
Donis
Ruben O
RO
Steffen
David J
DJ
Charleston
Bryan
B
Eskridge
Kent M
KM
Kelling
Clayton L
CL
D000818:Animals; D001831:Body Temperature; D001912:Bovine Virus Diarrhea-Mucosal Disease / Q000276:immunology*; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology / Q000473:pathology / Q000821:virology*; D001908:Diarrhea Viruses, Bovine Viral / Q000187:drug effects / Q000472:pathogenicity*; D005065:Euthanasia; D007370:Interferon Type I / Q000096:biosynthesis* / Q000097:blood; D019590:Nucleocapsid Proteins / Q000494:pharmacology*; D010581:Peyer's Patches / Q000473:pathology; D014765:Viral Vaccines / Q000276:immunology; D014774:Virulence / Q000187:drug effects*
D007370:Interferon Type I; D019590:Nucleocapsid Proteins; D014765:Viral Vaccines