doi: 10.15389/agrobiology.2018.2.248eng

UDC 636:619:578.833.3



A.G. Glotov, T.I. Glotova, S.V. Koteneva

Siberian Federal Scientific Center of Agro-BioTechnologies RAS, Institute of Experimental Veterinary Science of Siberia and the Far East, Federal Agency of Scientific Organizations, r.p. Krasnoobsk, PO box 463, Novosibirskii Region, Novosibirsk Province, 630501 Russia, e-mail (✉ corresponding author,,

Glotov A.G.
Koteneva S.V.
Glotova T.I.

Received July 5, 2017


Pestiviruses are an important cause of economic losses in the dairy and beef industry. Diseases caused by them are common around the world with varying prevalence associated with the features of regional strategy of livestock including in Russia (A.G. Glotov et al., 2002; M.I. Gulyukin et al., 2013; J.F. Ridpath, 2010). The bovine viral diarrhea virus is considered as a prototype member of the genus Pestivirus, Flaviviridae family. Two distinct viruses designated as BVDV1 and BVDV2 cause the disease in cattle. A candidate member of the genus is BVDV3, the atypical and not classified pestivirus which shows high similarity to BVDV1 and BVDV2. The BVDV3 presence in the cattle population can compromise BVDV control or eradication (F.V. Bauermann, 2013). This virus requires special attention. BVDV was isolated from commercial lots of fetal bovine serum used for cell culture and biologicals, and is dangerous because of possible spread to new regions (H. Schirrmeier et al., 2004). Viruses of this genus are contaminants of fetal serum, continuous cell line cultures, human and animal vaccines, interferons, trypsin, embryos, stem cells, etc. (B. Makoschey et al., 2003; S.Q. Zhang et al., 2014). Because of globalization and rapid development of cell biotechnology in veterinary and human medicine, the demand for fetal bovine serum, which is a by-product of beef industry, is annually increasing (G. Gstraunthaler et al., 2013). OIE has established product quality standards and regulations according to which all the cell cultures intended to use must be tested for the absence of the virus and its RNA in some passages. Blood serum including fetal serum must be free of the virus and also of the specific antibodies thereto (OIE, 2015). These requirements should also apply to BVDV3. The lack of fetal bovine serum production in Russia creates the possible risk of lots from foreign manufacturers of questionable quality. Special scholar publications report on cases of contamination of different cell cultures and sera by noncytopathic BVDV strains in Russia (S.V. Alekseenkova et al., 2013). The live vaccines prepared using low-quality raw materials can be a potential source of virus for susceptible animals, and contaminated diagnostic antigens can cause false results of the study. Thence, more strict control is extremely important to prevent biological contamination of vaccines and other biologicals.

Keywords: pestiviruses, cattle, bovine viral diarrhea viruses, atypical pestivirus, fetal bovine serum, contamination.


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  1. Ridpath J.F. Bovine viral diarrhea virus: global status. Veterinary Clinics of North America: Food Animal Practice, 2010, 26(1): 105-121 CrossRef
  2. Glotov A.G., Glotova T.I., Petrova O.G., Nefedchenko A.V., Tatarchuk A.T., Koteneva S.V., Vetrov G.V., Sergeev A.N. Veterinariya, 2002, 3: 17-21 (in Russ.).
  3. Gulyukin M.I., Yurov K.P., Glotov A.G., Donchenko N.A. Voprosy virusologii, 2013, 6: 13-18 (in Russ.).  
  4. Simmonds P., Becher P., Bukh J., Gould E.A., Meyers G., Monath T., Muerhoff S., Pletnev A., Hesse R.R., Smith D.B., Stapleton J.T., ICTV Report Consortium. ICTV virus Taxonomy profiles: FlaviviridaeJ. Gen. Virol., 2017, 98: 2-3 CrossRef
  5. Vilcek S., Durkovic B., Kolesarova M., Paton D.J. Genetic diversity of BVDV: consequences for classification and molecular epidemiology. Preventive Veterinary Medicine, 2005, 72: 31-35 CrossRef
  6. Pecora A., Malacari D.A., Ridpath J.F., Perez Aguirreburualde M.S., Combessies G., Odeón A.C., Romera S.A., Golemba M.D., Wigdorovitz A. First finding of genetic and antigenic diversity in 1b-BVDV isolates from Argentina. Res. Vet. Sci., 2014, 96(1): 204-222 CrossRef
  7. Deng M., Ji S., Fei W., Raza S., He C., Chen Y., Chen H., Guo Al. Prevalence study and genetic typing of bovine viral diarrhea virus (BVDV) in four bovine species in China. PLoS ONE, 2015, 10(7): e0134777 CrossRef
  8. Evermann J.F., Ridpath J.F. Clinical and epidemiologic observations of bovine viral diarrhea virus in the northwestern United States. Vet. Microbiol., 2002, 89(2-3): 129-139 CrossRef
  9. Carman S., Van Dreumel T., Ridpath J., Hazlett M., Alves D., Dubovi E., Tremblay R., Bolin S., Godkin A., Anderson N. Severe acute bovine viral diarrhea in Ontario, 1993-1995. J. Vet. Diagn. Invest., 1998, 10(1): 27-35 CrossRef
  10. Silveira S., Weber M.N., Mósena A.C., da Silva M.S., Streck A.F., Pescador C.A., Flores E.F., Weiblen R., Driemeier D., Ridpath J.F., Canal C.W. Genetic diversity of Brazilian bovine pestiviruses detected between 1995 and 2014. Transbound. Emerg. Dis., 2017, 64: 613-623 CrossRef
  11. Maya L., Puentes R., Reolón E., Acuña P., Riet F., Rivero R., Cristina J., Colina R. Molecular diversity of bovine viral diarrhea virus in Uruguay. Arch. Virol., 2016, 161(3): 529-535 CrossRef
  12. Tajima M., Frey H.R., Yamato O., Maede Y., Moennig V., Scholz H., Greiser-Wilke I. Prevalence of genotypes 1 and 2 of bovine viral diarrhea virus in Lower Saxony, Germany. Virus Res., 2001, 76(1): 31-42 CrossRef
  13. Novácková M., Jacková A., Kolesárová M., Vilcek S. Genetic analysis of a bovine viral diarrhea virus 2 isolate from Slovakia. Acta Virologica, 2008, 52(3): 161-166.
  14. Luzzago C., Lauzi S., Ebranati E., Giammarioli M., Moreno A., Cannella V., Masoero L., Canelli E., Guercio A., Caruso C., Ciccozzi M., De Mia G.M., Acutis P.L., Zehender G., Peletto S. Extended genetic diversity of bovine viral diarrhea virus and frequency of genotypes and subtypes in cattle in Italy between1995 and 2013. BioMed Res. Int., 2014, 2014: Article ID 147145 CrossRef
  15. Oem J.K., Hyun B.H., Cha S.H., Lee K.K., Kim S.H., Kim H.R., Park C.K., Joo Y.S. Phylogenetic analysis and characterization of Korean bovine viral diarrhea viruses. Vet. Microbiol., 2009, 139(3-4): 356-360 CrossRef
  16. Yamamoto T., Kozasa T., Aoki H., Sekiguchi H., Morino S., Nakamura S. Genomic analyses of bovine viral diarrhea viruses isolated from cattle imported into Japan between 1991 and 2005. Vet. Microbiol., 2008, 127(3-4): 386-371 CrossRef
  17. Ochirkhuu N., Konnai S., Odzaya B., Gansukh S., Murata S., Ohashi K. Molecular detection and characterization of bovine viral diarrhea virus in Mongolian cattle and yaks. Arch. Virol., 2016, 161(8): 2279-2283 CrossRef
  18. Giangaspero M., Harasawa R. Characterization of genotypes among bovine viral diarrhea virus type1 strains according to palindromic nucleotide substitutions in the genomic 5'-untranslated region. J. Virol. Methods, 2014, 195: 34-53 CrossRef
  19. Bauermann F.V., Ridpath J.F., Weiblen R., Flores E.F. HoBi-like viruses: an emerging group of pestiviruses. J. Vet. Diagn. Invest., 2013, 25(1): 6-15 CrossRef
  20. Glotov A.G., Glotova T.I. Atypical bovine pestiviruses (review). Agricultural Biology, 2015, 50(4): 399-408 CrossRef
  21. Schirrmeier H., Strebelow G., Depner K., Hoffmann B., Beer M. Genetic and antigenic characterization of an atypical pestivirus isolate, a putative member of a novel pestivirus species. J. Gen. Virol., 2004, 85: 3647-3652 CrossRef
  22. Weber M.N., Mosena A.C.S., Simoes S.V.D., Almeida L.L., Pessoa C.R., Budaszewski R.F., Silva T.R., Ridpath J.F., Riet-Correa F., Driemeier D., Canal C.W. Clinical presentation resembling mucosal disease associated with “HoBi”-like pestivirus in a field outbreak. Transbound. Emerg. Dis., 2016, 63(1): 92-100 CrossRef
  23. Mao L., Li W., Zhang W., Yang L., Jiang J. Genome sequence of a novel Hobi-like pestivirus in China. J. Virol., 2012, 86(22): 12444 CrossRef
  24. Haider N., Rahman M.S., Khan S.U., Mikolon A., Gurley E.S., Osmani M.G., Shanta I.S., Paul S.K., Macfarlane-Berry L., Islam A., Desmond J., Epstein J.H., Daszak P., Azim T., Luby S.P., Zeidner N., Rahman M.Z. Identification and epidemiology of a rare HoBi-like pestivirus strain in Bangladesh. Transbound. Emerg. Dis., 2014, 61: 193-198 CrossRef
  25. Mishra N., Rajukumar K., Pateriya A., Kumar M., Dubey P., Behera S.P., Verma A., Bhardwaj P., Kulkarni D.D., Vijaykrishna D., Reddy N.D. Identification and molecular characterization of novel and divergent HoBi-like pestiviruses from naturally infected cattle in India. Vet. Microbiol., 2014, 174: 239-246 CrossRef
  26. Decaro N., Lucente M.S., Mari V., Uttenthal A., Polak M.P., Ståhl K., Alenius S., Shan H., Yin H., Belák S. Atypical pestivirus and severe respiratory disease in calves, Europe. Emerg. Infect. Dis., 2011, 17(8): 1549-1552 CrossRef
  27. Giammarioli M., Ridpath J.F., Rossi E., Bazzucchi M., Casciari C., De Mia G.M. Genetic detection and characterization of emerging HoBi-like viruses in archival foetal bovine serum batches. Biologicals, 2015, 43(4): 220-224 CrossRef
  28. Gstraunthaler G., Lindl T., van der Valk J. A plea to reduce or replace fetal bovine serum in cell culture media. Cytotechnology, 2013, 65(5): 791-793 CrossRef
  29. Gstraunthaler G. Alternatives to the use of fetal bovine serum: serum-free cell culture. ALTEX, 2003, 20(4): 275-281.
  30. Flatschart R.B., Caldas L.A., Almeida D.O., dos Santos N.C., Boldrini L.C., Granjeiro J.M., Folgueras-Flatschart A.V. The Impact of BVDV presence on fetal bovine serum used in the biotechnology industry. In: Advances in medicine and biology. Nova Biomedical, New York, 2016. V. 95: 75-95.
  31. Zhang S.Q., Guo B.T.L., Wang F.X., Zhu H.W., Wen Y.J., Cheng S. Genetic diversity of bovine viral diarrhea viruses in commercial bovine serum batches of Chinese origin. Infection, Genetics and Evolution, 2014, 27: 230-233 CrossRef
  32. Häusl P. Fetal Bovine Serum running short. European Biotechnology — Life Sciences and Industry Magazine, 2008. Available No date.
  33. Market Research Reports. Cell Culture Market by Equipment — Global Forecast to 2018. Available No date.
  34. BCC Research. Global Markets for Media, Sera and Reagents in Biotechnology. 2015. Available No date.
  35. Market Research Reports. Cell Expansion Market by Product — Forecast to 2019. Available No date.
  36. Davis D., Hirschi S.D. Fetal bovine serum: what you should ask your supplier and why. BioProcess. J., 2014, 13(1): 19-21 CrossRef      
  37. Makoschey B., van Gelder P.T., Keijsers V., Goovaerts D. Bovine viral diarrhoea virus antigen in foetal calf serum batches and consequences of such contamination for vaccine production. Biologicals, 2003, 31(3): 203-208 CrossRef
  38. EMA. Guideline on the use of bovine serum in the manufacture of human biological medicinal products. 2013. Available Accessed April 09, 2018.
  39. Siegel W., Foster L. Fetal bovine serum: the impact of geography. BioProcess. J., 2013, 12(3): 28-30 CrossRef
  40. Xia H., Vijayaraghavan B., Belák S., Liu L. Detection and identification of the atypical bovine pestiviruses in commercial foetal bovine serum batches. PLoS ONE, 2011, 6(12): e28553 CrossRef
  41. Bauermann F.V., Harmon A., Flores E.F., Falkenberg S.M., Reecy J.M., Ridpath J.F. In vitro neutralization of HoBi-like viruses by antibodies in serum of cattle immunized with inactivated or modified live vaccines of bovine viral diarrhea viruses 1 and 2. Vet. Microbiol., 2013, 166(1-2): 242-245 CrossRef
  42. Bauermann F.V., Flores E.F., Falkenberg S.M., Weiblen R., Ridpath J.F. Lack of evidence for the presence of emerging HoBi-like viruses in North American fetal bovine serum lots. J. Vet. Diagn. Invest., 2014, 26(1): 10-17 CrossRef
  43. Daryany M.K.A., Hosseini S.M., Raie M., Fakharie J., Zareh A. Study on continuous (254 nm) and pulsed UV (266 and 355 nm) lights on BVD virus inactivation and its effects. Journal of Photochemistry and Photobiology B: Biology, 2009, 94(2): 120-124 CrossRef
  44. Ceylan C., Severcan F., Ozkul A., Severcan M., Bozoglu F., Taheri N. Biophysical and microbiological study of high hydrostatic pressure inactivation of Bovine Viral Diarrhea virus type 1 on serum. Vet. Microbiol., 2012, 154(3-4): 266-271 CrossRef
  45. Hodgson J. To treat or not to treat: that is the question for serum. Bio/Technology, 1995, 13(4): 333-343 CrossRef
  46. OIE. Manual of diagnostic tests and vaccines for terrestrial animals. P. 2, S. 2.4. Ch. 2.4.8. Bovine viral diarrhoea. Paris, France, 2015.
  47. Flatschart R.B., Caldas L.A., de Oliveira Almeida D., Correeia dos Santos N., da Cunha Boldrini L., Granjeiro M.J., Flatschart A.V.F. The impact of BVDV presence on fetal bovine serum used in the biotechnology industry. In: Advances in Medicine and Biology. L.V. Berhardt (ed.). Nova Science Publishers, Inc., 2016, V. 95, Chapter 4: 75-93.
  48. Alekseenkova S.V., Yurov G.K., Gal'nbek T.V., Kalita I.A., Yurov K.P. Rossiiskii veterinarnyi zhurnal, 2013, 1: 15-18 (in Russ.).
  49. Uryvaev L.V., Ionova K.S., Dedova A.V., Dedova L.V., Selivanova T.K., Parasyuk N.A., Mezentseva M.V., Kostina L.V., Gushchina E.A., Podchernyaeva R.Ya., Grebennikova T.V. Voprosy virusologii, 2012, 5(57): 15-21 (in Russ.).
  50. Koteneva S.V., Maksyutov R.A., Glotova T.I., Glotov A.G.Identification of the bovine atypical pestivirus in biological samples. Agricultural Biology, 2017, 52(6): 1259-1264 CrossRef