Metagenomic analysis reveals presence of different animal viruses in commercial fetal bovine serum and trypsin

Zool Res. 2022 Sep 18;43(5):756-766. doi: 10.24272/j.issn.2095-8137.2022.093.

Abstract

Animal-derived biological products, such as fetal bovine serum (FBS) and trypsin, are important supplements for scientific, pharmaceutical, and medical use. Although preventive guidelines and tests are implemented to reduce potential viral contamination in these biologicals, they do not target unusual or emerging viruses, leading to safety concerns. Using unbiased metagenomics, we investigated the presence of viruses in recently collected commercial FBS and trypsin samples from different geographic regions. In total, we detected viral sequences belonging to Parvoviridae, Anelloviridae, Flaviviridae, Herpesviridae, Caliciviridae, Nodaviridae, Rhabdoviridae, and Paramyxoviridae, including several viruses related to bovine diseases, viruses of potential human and insect origin, and viruses of unknown origin. Bovine parvovirus 3 and bosavirus were detected with high frequency and abundance in FBS, necessitating more stringent testing for these parvoviruses during production. Both bovine norovirus and bovine viral diarrhea virus 1 displayed relatively high genetic distance to closest hits, indicating the presence of new genotypes in farm animals. While the origin of novel lyssavirus and Nipah virus is unclear, their presence raises the possibility of the introduction of pathogenic animal-derived viruses into biologicals. Our results showed relatively widespread contamination of different viruses in biologicals, underscoring the need for robust safety protocol alternatives, such as metagenomic sequencing, to monitor emerging viruses.

动物源性的生物制品,如胎牛血清(FBS)和胰蛋白酶(Trypsin),是科学、制药和医疗等领域的重要添加成分。尽管采取了预防性的指南和措施来减少这些生物制品中潜在的病毒污染,但是这些措施并未针对罕见的或新发的病毒,因此可能会导致潜在的安全问题。我们使用无偏的宏基因组方法,对来自不同区域的商业FBS和Trypsin样本中携带的病毒进行了分析。我们检测到了 Parvoviridae、Anelloviridae、Flaviviridae、Herpesviridae、Caliciviridae、Nodaviridae、RhabdoviridaeParamyxoviridae的病毒序列。这些序列中包括几种与牛疾病相关的病毒、潜在人类和昆虫来源的病毒以及一些来源不明的病毒。牛细小病毒3型(BPV3)和bosavirus在FBS中的检出频率最高、数量最多,暗示了在生产过程中需要对这些细小病毒进行更严格的检测。牛诺如病毒和牛病毒性腹泻病毒(BVDV)与其最接近的毒株均显示出相对较高的遗传距离,表明这些样本来源的动物中可能存在新的病毒基因型。样本中发现了潜在的新型狂犬病毒和尼帕病毒序列,虽然它们可能是未知来源的污染造成,但是这些病毒序列的存在也暗示了一些重要的致命性的动物病毒被引入到生物制品中的风险。这些结果表明生物制品中存在着普遍的病毒序列污染,因此未来需要更加强有力的措施,如宏基因组测序等方法作为质量和安全控制的替代方案,并同时来监测可能出现的新发病毒。.

Keywords: Biosafety; FBS; Trypsin; Viral contaminations; Virome.

MeSH terms

  • Animals
  • Humans
  • Metagenomics / methods
  • Phylogeny
  • Serum Albumin, Bovine* / genetics
  • Trypsin / genetics
  • Viruses* / genetics

Substances

  • Serum Albumin, Bovine
  • Trypsin

Associated data

  • GENBANK/OM836168-OM836182, OM816743, OM817465, OM817500, ON695913

Grants and funding

This work was supported by the National Natural Science Foundation of China (32170147, 31900158)