title: Role of bovine viral diarrhea virus biotype in the establishment of fetal infections.
abstract: OBJECTIVE
  To examine the role of bovine viral diarrhea virus (BVDV) biotype on the establishment of fetal infection in cattle.
  
  
  METHODS
  30 mixed-breed pregnant cows.
  
  
  METHODS
  Pregnant cows were inoculated oronasally with either i-WNADL, originating from an infectious BVDV cDNA clone of the National Animal Disease Laboratory (NADL) isolate, or the parental virus stock, termed NADL-A.
  
  
  RESULTS
  All cows developed neutralizing antibodies to BVDV, and virus was commonly isolated from peripheral blood mononuclear cells or nasal swab specimens of NADL-A inoculated cows; however, virus was rarely isolated from specimens of i-WNADL inoculated cows. i-WNADL did not cause fetal infection, whereas all fetuses harvested from NADL-A inoculated cows at 6 weeks after inoculation had evidence of infection. Immunoblot analysis of fetal virus isolates revealed the absence of NS3, confirming a noncytopathic (NCP) biotype BVDV in the NADL-A stock. The sequence of the NCP contaminant (termed NADL-1102) and the i-WNADL genome were virtually identical, with the exception of a 270 nucleotide-long insert in the i-WNADL genome. Phylogenetic analyses revealed that NADL-1102 forms a monophyletic group with 6 other NADL genomes.
  
  
  CONCLUSIONS
  These data suggest that the contaminating NCP virus in the NADL-A stock was the ancestral NADL virus, which originally infected a bovine fetus and recombined to produce a cytopathic (CP) variant. Following oronasal infection of pregnant cows, viremia and transplacental transmission of CP BVDV to the fetus is rare, compared with the high occurrence of maternal viremia and fetal infection observed with NCP BVDV.
authors.affiliation: Pfizer Animal Health Research and Development, Groton, CT 06340, USA.
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Harding
authors.forename: Xuemei
authors.initials: X
authors.lastname: Cao
authors.forename: Homayoun
authors.initials: H
authors.lastname: Shams
authors.forename: Anthony F
authors.initials: AF
authors.lastname: Johnson
authors.forename: Ventzislav B
authors.initials: VB
authors.lastname: Vassilev
authors.forename: Laura H
authors.initials: LH
authors.lastname: Gil
authors.forename: David W
authors.initials: DW
authors.lastname: Wheeler
authors.forename: Deborah
authors.initials: D
authors.lastname: Haines
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Sibert
authors.forename: Lynn D
authors.initials: LD
authors.lastname: Nelson
authors.forename: Manuel
authors.initials: M
authors.lastname: Campos
authors.forename: Ruben O
authors.initials: RO
authors.lastname: Donis
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D001483:Base Sequence; D001912:Bovine Virus Diarrhea-Mucosal Disease / Q000276:immunology / Q000635:transmission* / Q000821:virology*; D002417:Cattle; D018076:DNA, Complementary / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D001908:Diarrhea Viruses, Bovine Viral / Q000145:classification* / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D005260:Female; D005333:Fetus / Q000276:immunology / Q000821:virology*; D018445:Infectious Disease Transmission, Vertical / Q000662:veterinary; D010802:Phylogeny; D011247:Pregnancy; D014766:Viremia; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D018076:DNA, Complementary; D004279:DNA, Viral