BRSV and RSV translational model

BRSV

Wageningen Bioveterinary Research (WBVR) conducts extensive research into the immunopathology of Bovine Respiratory Syncytial Virus (BRSV).

What is BRSV?

This virus is an important pathogen in cattle. It causes cold-like symptoms in adult animals, while in calves it infects the small airways, causing bronchiolitis or pneumonia. The virus causes outbreaks of this respiratory disease annually, particularly in calves up to the age of six months.

How does the virus spread?

Almost all cattle will have been infected with SCSV before their second year. Infections and re-infections mainly occur in the autumn and winter. Spreading of the virus is rarely seen at other times of the year, and the virus seems to survive in a dormant form within the population.

What are the symptoms?

BRSV can be particularly severe in young animals, where it often causes fever (body temperature above 39.5ºC), rapid breathing, breathing difficulties and abdominal breathing. The clinical symptoms usually start with coughing and nasal discharge. If the small airways are also affected, expiratory wheezing, rapid breathing and signs of shortness of breath, as well as cyanosis and forced breathing (active involvement of the rib and abdominal muscles on inhalation) are observed. Clinical symptoms coinciding with bronchiolitis and/or pneumonia are serious and are very likely to be fatal.

How do you control BRSV?

To control and prevent the disease, it is necessary to understand how the body ultimately protects itself against the virus. It is therefore important to know what the consequences of the infection are for the body and how the body's immune system reacts. After a natural infection or after vaccination, for example, virus-specific antibodies are produced as part of the specific immune system. An effective immune response means that the animal is protected against a potential (re)infection, but in some cases a non-effective immune response can also be induced. Plenty of cases are known in which, for example, infected vaccinated calves showed much more severe symptoms than unvaccinated ones. WBVR is conducting extensive research into the role of the immune system during the course of the clinical infection.

How does WBVR detect the virus?

Direct detection of virus in secretions from the airways using immunofluorescence or with the aid of a PCR test is generally the fastest method of diagnosis. The virus can also be isolated from patient material (nasal/throat swabs, lung flushes or lung tissue from autopsy). The patient material is then transferred to virus-sensitive cells, on which a characteristic abnormal effect can be observed after a few days to a week. Specific antibodies produced to combat the virus can be detected with an ELISA or virus neutralisation test (VNT).

Is there a vaccine available?

Different types of vaccines are available: live/attenuated or inactivated virus vaccines, vaccines with one or more components and possible combinations (multiple components, live/attenuated and inactivated), all with vaccine-specific advantages and disadvantages. None of the current vaccines seems to be able to prevent an animal from becoming infected.

Read our publications on BRSV

Cortjens, B., de Jong, R., Bonsing, J. G., van Woensel, J. B. M., Bem, R. A., & Antonis, A. F. G. (2019). Human respiratory syncytial virus infection in the pre-clinical calf model. Comparative Immunology, Microbiology and Infectious Diseases, 65, 213-218

Cortjens B, de Jong R, Bonsing JG, van Woensel JBM, Antonis AFG, Bem RA. Local dornase alfa treatment reduces NETs-induced airway obstruction during severe RSV infection. Thorax. 2018 Jun;73(6):578-580.

Cortjens, B., de Boer, O.J., de Jong, R., Antonis, A.F., Sabogal Pineros, Y.S., Lutter, R., van Woensel, J.B., Bem, R.A. (2016). Neutrophil extracellular traps cause airway obstruction during respiratory syncytial virus disease. The Journal of pathology 238, 401-411.

Antonis, A.F.G.; Jong, M.C. de; Poel, W.H.M. van der; Most, R.G. van der; Stockhofe-Zurwieden, N.; Kimman, T.G.; Schrijver, R.S. (2010); Age-dependent differences in the pathogenesis of bovine respiratory syncytial virus infections related to the development of natural immunocompetence; Journal of General Virology 91 . - p. 2497 - 2506.

Antonis, A.F.G.; Most, R.G. van der; Suezer, Y.; Stockhofe-Zurwieden, N.; Daus, F.J.; Sutter, G.; Schrijver, R.S. (2007); Vaccination with recombinant modified vaccinia virus Ankara expressing bovine respiratory syncytial virus (bRSV) proteins protects calves against RSV challenge; Vaccine 25 (25). - p. 4818 - 4827.

Vangeel, I.; Antonis, A.F.G.; Fluess, M.; Peters, A.R.; Harmeyer, S.S. (2007); Efficacy of a modified live intranasal bovine respiratory syncytial virus vaccine in 3-week-old calves experimentally challenged with BRSV; The Veterinary Journal 174 (3). - p. 627 - 635.

Antonis, A.F.G.; Claassen, E.A.W.; Hensen, E.J.; Groot, R.J. de; Groot-Mijnes, J.D.F. de; Schrijver, R.S.; Most, R.G. van der (2006); Kinetics of antiviral CD8 T cell responses during primary and post-vaccination secondary bovine respiratory syncytial virus infection; Vaccine 24 (10). - p. 1551 - 1561.

Valentova, V.; Antonis, A.F.G.; Kovarcik, K. (2005); Restriction enzyme analysis of RT-PCR amplicons as a rapid method for detection of genetic diversity among bovine respiratory syncytial virus isolates; Veterinary Microbiology 108 (1-2). - p. 1 - 12.

Vangeel, I.; Antonis, A.F.G.; Fluess, M.; Peters, A.R.; Harmeyer, S.S. (2005); Efficacy of a modified live intranasal bovine respiratory syncytial virus vaccine in three-week-old calves experimentally challenged with BRSV; Cattle practice: The Journal of the British Cattle Veterinary Association 174 (13). - p. 263 - 271.

Soethout, E.C.; Antonis, A.F.G.; Ulfman, L.H.; Hoek, A. van; Most, R.G. van der; Muller, K.E.; Rutten, V. (2004); Bovine respiratory syncytial virus infection influences the impact of alpha 4- and beta(2)-integrin-mediated adhesion of peripheral blood neutrophils; Clinical and Experimental Immunology 138 (3). - p. 388 - 395.

Antonis, A.F.G.; Schrijver, R.S.; Daus, F.J.; Steverink, M.; Stockhofe, N.; Langedijk, J.P.; Most, R.G. van der (2003); Vaccine-induced immunopathology during bovine respiratory syncytial virus infection: exploring the parameters of pathogenesis; Journal of Virology 77 (22). - p. 12067 - 12073.

Mars, M.H.; Bruschke, C.J.M.; Oirschot, J.T. van (1999); Airborne transmission of BHV1, BRSV, and BVDV among cattle is possible under experimental conditions; Veterinary microbiology 66, 1999, 197-207

Van der Poel WHM, Middel WGJ, Schukken YH (1999) Antibody titer against bovine respiratory syncytial virus in colostrum-fed dairy calves born in various seasons. Am J Vet Res 60: 1098-1101.

Bosch JC, Frankena K, Franken P, Hage JJ, De Jong MCM, Kaashoek MJ, Maris-Veldhuis MA, Noordhuizen JPTM, Van der Poel WHM, Verhoeff J, Weerdmeester K, Zimmer GM and Van Oirschot JT (1998) Bovine herpesvirus 1 marker vaccines reduce the incidence of infections. Vaccine 16: 265-271.

Knott I, Weynants V, Walravens K, Van der Poel WHM, Kramps JA, Letteson JJ (1998) Immune response of calves experimentally infected with non-cell-culture-passaged bovine respiratory syncytial virus. Arch Virol 143: 1119-1128

Schrijver, R.S.; Langedijk, J.P.M.; Keil, G.M.; Middel, W.G.J.; Maris-Veldhuis, M.; Oirschot, J.T. van; Rijsewijk, F.A.M. (1998); Comparison of DNA application methods to reduce BRSV shedding in cattle; Vaccine 16, 1998, 130-134. Also in: Thesis, 1997, ch 9

Van der Poel WHM, Langedijk JPM, Kramps JA, Brand A, Middel WGJ, Van Oir­schot JT (1997) Serological indication for persisten­ce of bovine respira­tory syncytial virus in cattle and atempts to detect the virus. Arch Virol 142: 1681-1696.

Schrijver, R.S.; Langedijk, J.P.M.; Keil, G.M.; Middel, W.G.J.; Maris-Veldhuis, M.; Kramps, J.A.; Oirschot, J.T. van; Rijsewijk, F.A.M. (1997); Immunization of cattle with a BHV1 vector vaccine or a DNA vaccine both coding for the G protein of BRSV; Vaccine 15, 1997, 1908-1915.

Schrijver, R.S.; Hensen, E.J.; Langedijk, J.P.M.; Daus, F.; Middel, W.G.J.; Kramps, J.A.; Oirschot, J.T. van (1997); Antibody responses against epitopes on the F protein of bovine respiratory syncytial virus differ in infected or vaccinated cattle; Archives of virology 142, 1997, 2195-2210.

Prozzi, D.; Walravens, K.; Langedijk, J.P.; Daus, F.; Kramps, J.A.; Letesson, J.J. (1997); Antigenic and molecular analyses of the variability of bovine respiratory syncytial virus G glycoprotein; Journal of general virology 78, 1997, 359-366

De Jong MCM, Van der Poel WHM, Kramps JA, Brand A, Van Oirschot JT (1996) A quantitative investigation into outbreaks of bovine respiratory syncy­tial virus infecti­ons in cattle herds. American Journal of Veterinary Research 57: 628-633.

Van der Poel WHM, Schrijver RS, Middel WGJ, Kramps JA, Brand A, Van Oirschot JT (1996) Experimental reproduction of respiratory disease in calves with non-cell-culture-passaged bovine respiratory syncytial virus. The Veterina­ry Quarterly 18: 81-86.

Schrijver RS, Langedijk JPM, Van der Poel WHM, Middel WGJ, Kramps JA, Van Oirschot JT (1996) Antibody responses to the G and F protein of bovine respiratory syncytial virus after experimental and natural infections. Clin Diagn Lab Immunol 3: 500-506.

Langedijk, J.P.M.; Middel, W.G.J.; Schaaper, W.M.M.; Meloen, R.H.; Kramps, J.A.; Brandenburg, A.H.; Oirschot, J.T. van (1996); Type-specific serologic diagnosis of respiratory syncytial virus infection, based on a synthetic peptide of the attachment protein G; Journal of immunological methods 193, 1996, 157-166

Schrijver, R.S.; Daus, E.; Kramps, J.A.; Langedijk, J.P.M.; Buijs, R.; Middel, W.G.J.; Taylor, G.; Furze, J.; Huyben, M.W.C.; Oirschot, J.T. van (1996); Subgrouping of bovine respiratory syncytial virus strains detected in lung tissue; Veterinary microbiology 53, 1996, 253-260

Poel, W.H.M. van der; Schrijver, R.S.; Middel, W.G.J.; Kramps, J.A.; Brand, A.; Oirschot, J.T. van (1996); Experimental reproduction of respiratory disease in calves with non-cell-culture-passaged bovine respiratory syncytial virus; Veterinary quarterly 18, 1996, 81-86

Van der Poel WHM, Mourits MCM, Nielen N, Frankena K, Van Oirschot JT, and Schuk­ken YH (1995) Respiratory syncytial virus reinfections and decreased milk yield in dairy cattle. The Veterinary Quarterly 17: 77-81.

Van der Poel WHM, Langedijk JPM, Kramps JA, Middel WGJ, Van Oirschot JT. (1995) Bovine respiratory syncytial virus antibodies in sera of non-bovine species. Archives of Virology 140: 1549-1555.

Van der Poel WHM, Brand A, Kramps JA, Van Oirschot JT (1994) Respiratory syncytial virus infections in human beings and in cattle, an epidemiolo­gical review. Journal of infection 29: 215-228

Van der Poel WHM, Kramps JA, Middel WGJ, Van Oirschot JT, Brand A (1993) Dynamics of bovine respiratory syncytial virus: a longitudinal epidemio­logical study in dairy herds. Archives of Virology 133: 309-321

Kimman TG, Westenbrink F. Immunity to human and bovine respiratory syncytial virus. Arch Virol. 1990;112(1-2):1-25. Review.

Kimman TG, Sol J, Westenbrink F, Straver PJ. A severe outbreak of respiratory tract disease associated with bovine respiratory syncytial virus probably enhanced by vaccination with modified live vaccine; Vet Q. 1989 Oct;11(4):250-3.

Westenbrink F, Straver PJ, Kimman TG, de Leeuw PW. Development of a neutralising antibody response to an inoculated cytopathic strain of bovine virus diarrhoea virus. Vet Rec. 1989 Sep 2;125(10):262-5. Erratum in: Vet Rec 1989 Nov 11;125(20):499.

Kimman TG, Westenbrink F, Straver PJ. Priming for local and systemic antibody memory responses to bovine respiratory syncytial virus: effect of amount of virus, virus replication, route of administration and maternal antibodies. Vet Immunol Immunopathol. 1989 Sep;22(2):145-60.

Kimman TG, Daha MR, Brinkhof JM, Westenbrink F. Activation of complement by bovine respiratory syncytial virus-infected cells. Vet Immunol Immunopathol. 1989 Jul;21(3-4):311-25.

Kimman TG, Terpstra GK, Daha MR, Westenbrink F. Pathogenesis of naturally acquired bovine respiratory syncytial virus infection in calves: evidence for the involvement of complement and mast cell mediators. Am J Vet Res. 1989 May;50(5):694-700.

Kimman TG, Straver PJ, Zimmer GM. Pathogenesis of naturally acquired bovine respiratory syncytial virus infection in calves: morphologic and serologic findings. Am J Vet Res. 1989 May;50(5):684-93.

Westenbrink F, Kimman TG, Brinkhof JM. Analysis of the antibody response to bovine respiratory syncytial virus proteins in calves. J Gen Virol. 1989 Mar;70 ( Pt 3):591-601.

ter Laak EA, Schreuder BE, Kimman TG, Houwers DJ; Ovine keratoconjunctivitis experimentally induced by instillation of Mycoplasma conjunctivae. Vet Q. 1988 Oct;10(4):217-24.

Kimman TG, Zimmer GM, Westenbrink F, Mars J, van Leeuwen E. Epidemiological study of bovine respiratory syncytial virus infections in calves: influence of maternal antibodies on the outcome of disease. Vet Rec. 1988 Jul 23;123(4):104-9.

Kimman TG, Westenbrink F, Straver PJ, Van Zaane D, Schreuder BE. Isotype-specific ELISAs for the detection of antibodies to bovine respiratory syncytial virus. Res Vet Sci. 1987 Sep;43(2):180-7.

Westenbrink F, Kimman TG. Immunoglobulin M-specific enzyme-linked immunosorbent assay for serodiagnosis of bovine respiratory syncytial virus infections. Am J Vet Res. 1987 Jul;48(7):1132-7.

Kimman TG, Westenbrink F, Schreuder BE, Straver PJ. Local and systemic antibody response to bovine respiratory syncytial virus infection and reinfection in calves with and without maternal antibodies. J Clin Microbiol. 1987 Jun;25(6):1097-106.

Kimman TG, Zimmer GM, Straver PJ, de Leeuw PW. Diagnosis of bovine respiratory syncytial virus infections improved by virus detection in lung lavage samples. Am J Vet Res. 1986 Jan;47(1):143-7.