Isolation of a naturally occurring vaccine/wild-type recombinant bovine herpesvirus type 1 (BoHV-1) from an aborted bovine fetus. Issue 32 (26th July 2019)

• Record Type: Journal Article
• Authors: d'Offay, Jean M.; Fulton, Robert W.; Fishbein, Mark; Eberle, R.; Dubovi, Edward J.
• Is Part Of: Vaccine. Volume 37:Issue 32(2019)
• Page Start: 4518
• Page End: 4524
• Publication Date: 2019-07-26
• Subjects: BoHV-1 -- Bovine herpesvirus type 1 -- Wild-type -- Vaccine/wild-type recombinant -- Vaccine-derived isolates -- MLV viruses -- SNP patterns; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2019.06.059
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Complete genomes of six 1978/79 fetal and respiratory BoHV-1 isolates were sequenced. Vaccine-derived strains, WTs, and one vaccine/WT recombinant virus were recovered. Fetal recombinant had a WT genome with two blocks of vaccine-derived sequences. Evidence that recombination can occur naturally between BoHV-1 vaccine and WT viruses. Underscores importance of gene-deleted marker vaccines recombining and losing markers. Abstract: Bovine herpesvirus type 1 (BoHV-1) causes various disease syndromes in cattle including respiratory disease and abortions. During an investigation into the potential role of BoHV-1 modified-live vaccines (MLV) causing diseases in cattle, we performed whole genome sequencing on six BoHV-1 field strains isolated at Cornell Animal Health Diagnostic Center in the late 1970s. Three isolates (two respiratory and a fetal) were identified as vaccine-derived isolates, having SNP patterns identical to that of a previously sequenced MLV virus that exhibited a deleted US2 and truncated US1.67 genes. Two other isolates (a respiratory and a fetal) were categorized as wild-type (WT) viruses based on their unique SNP pattern that is distinct from MLV viruses. The sixth isolate from an aborted fetus was a recombinant virus with 62% of its genome exhibiting SNPs identical to one of the above-mentioned WT viruses also recovered from an aborted fetus. The remaining 38% consisted of two blocks of sequences derived from the MLV virus. The first block replaced the UL9-UL19 region, and the second vaccine-derived sequence block encompassed all the genes within the unique short region and the internal/terminal repeats containing the regulatory genes BICP4 and BICP22. This is confirmatory evidence that recombination between BoHV-1 MLV and WT viruses can occur under natural conditions and cause disease. It is important in that it underscores the potential for the glycoprotein E negative (gE − ) marker vaccine used to eradicate BoHV-1 in some countries, to recombine with virulent field strains allowing them to capture the gE − marker, thereby endangering the control and eradication programs.