Role of bovine viral diarrhea virus biotype in the establishment of fetal infections

Martha J. Harding Pfizer Animal Health Research and Development, Eastern Point Rd, Groton, CT 06340.
Present address is Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520-8016.

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Xuemei Cao Pfizer Animal Health Research and Development, Eastern Point Rd, Groton, CT 06340.

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Homayoun Shams Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583.
Present address is Center for Pulmonary and Infectious Diseases Control, University of Texas Health Center, Tyler, TX 75708-3154.

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Anthony F. Johnson Pfizer Animal Health Research and Development, Eastern Point Rd, Groton, CT 06340.

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Ventzislav B. Vassilev Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583.

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Laura H. Gil Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583.

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David W. Wheeler Pfizer Animal Health Research and Development, Eastern Point Rd, Groton, CT 06340.

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Deborah Haines Department of Veterinary Microbiology, Western College of Veterinary Medicine, Saskatoon, SA, Canada S7N-5B4.

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Gary J. Sibert Pfizer Animal Health Research and Development, Eastern Point Rd, Groton, CT 06340.

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Lynn D. Nelson Pfizer Animal Health Research and Development, Eastern Point Rd, Groton, CT 06340.

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Manuel Campos Pfizer Animal Health Research and Development, Eastern Point Rd, Groton, CT 06340.
Present address is Immunaxis Inc, 94 Redwood Meadows Dr, Redwood Meadows, AB, Canada T3Z 1A3.

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Ruben O. Donis Department of Veterinary and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583.

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Abstract

Objective—To examine the role of bovine viral diarrhea virus (BVDV) biotype on the establishment of fetal infection in cattle.

Animals—30 mixed-breed pregnant cows.

Procedure—Pregnant cows were inoculated oronasally with either i-VVNADL, 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-VVNADL inoculated cows. i-VVNADL 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-VVNADL genome were virtually identical, with the exception of a 270 nucleotide-long insert in the i-VVNADL genome. Phylogenetic analyses revealed that NADL-1102 forms a monophyletic group with 6 other NADL genomes.

Conclusions and Clinical Relevance—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. (Am J Vet Res 2002;63:1455–1463)

Abstract

Objective—To examine the role of bovine viral diarrhea virus (BVDV) biotype on the establishment of fetal infection in cattle.

Animals—30 mixed-breed pregnant cows.

Procedure—Pregnant cows were inoculated oronasally with either i-VVNADL, 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-VVNADL inoculated cows. i-VVNADL 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-VVNADL genome were virtually identical, with the exception of a 270 nucleotide-long insert in the i-VVNADL genome. Phylogenetic analyses revealed that NADL-1102 forms a monophyletic group with 6 other NADL genomes.

Conclusions and Clinical Relevance—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. (Am J Vet Res 2002;63:1455–1463)

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