Metagenomic assessment of adventitious viruses in commercial bovine sera

Animal serum is an essential supplement for cell culture media. Contamination of animal serum with adventitious viruses has led to major regulatory action and product recalls. We used metagenomic methods to detect and characterize viral contaminants in 26 bovine serum samples from 12 manufacturers. Across samples, we detected sequences with homology to 20 viruses at depths of up to 50,000 viral reads per million. The viruses detected represented nine viral families plus four taxonomically unassigned viruses and had both RNA genomes and DNA genomes. Sequences ranged from 28% to 96% similar at the amino acid level to viruses in the GenBank database. The number of viruses varied from zero to 11 among samples and from one to 11 among suppliers, with only one product from one supplier being entirely "clean." For one common adventitious virus, bovine viral diarrhea virus (BVDV), abundance estimates calculated from metagenomic data (viral reads per million) closely corresponded to Ct values from quantitative real-time reverse transcription polymerase chain reaction (rtq-PCR), with metagenomics being approximately as sensitive as rtq-PCR. Metagenomics is useful for detecting taxonomically and genetically diverse adventitious viruses in commercial serum products, and it provides sensitive and quantitative information.