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Professor A. (Andrea) Gröne, PhD

Wednesday 26 September 2012

Virus-host interactions in the veterinary field: friend or foe?

Head: Prof. Dr. A. (Andrea) Gröne, DVM, PhD
Principle investigator: Dr. M.H. (Hélène) Verheije, PhD

Viruses interact with their host on many different levels and the nature of each of these interactions ultimately determines the outcome of an infection. Understanding virus-host interactions is crucial to understand virus pathogenesis, but also to ultimately be able to combat the virus infection by vaccines or antivirals. On the other hand, one can exploit virus-host interactions, for example to combat important diseases like cancer. Within the Pathobiology research group of the Faculty of Veterinary Medicine we focus on the elucidation of coronavirus-host interactions in order to counteract or exploit these features for the benefit of both companion and production animals. Currently, two research projects are running:

Redirected coronaviruses as anti-tumor therapy Cancer is the number one cause of death in companion animals. For many cancers, however, no effective cure is available and new therapies are wanted. One innovative therapeutic option is the use of viruses to kill tumor cells. To design tumor-selective oncolytic viruses specific targeting of the viruses to antigens (over)expressed on tumor cells is often required. In collaboration with the Virology department of the Veterinary Faculty we have previously provided proof of principle for redirecting MHV to human tumor cells with subsequent in vitro and in vivo infection and tumor cell killing. Currently, we are extrapolating this research line towards tumors of small companion animals in collaboration with the Department Companion Animals. Focus lies on the specific redirection of MHV towards canine tumor cells and includes both optimization of the viral vector platform and the elucidation of specific cell surface markers on companion animal tumors. In addition, we aim at improving the imaging of tumors in dogs, a project which is excecuted in collaboration with the Science Faculty, Department Cell biology. Ultimately, we aim at developing new therapeutic agents and imaging modalities against canine and other companion animals.

Key papers:
Targeting non-human coronaviruses to human cancer cells using a bispecific single-chain antibody. Gene Therapy. 2005; 12(18):1394-404

Soluble receptor-mediated targeting of mouse hepatitis coronavirus to the human epidermal growth factor receptor. J Virol. 2005; 79(24):15314-22

Redirecting coronavirus to a nonnative receptor through a virus-encoded targeting adapter. J Virol. 2006; 80(3):1250-60

Antibody-mediated targeting of viral vectors to the Fc receptor expressed on acute myeloid leukemia cells. Leukemia. 2006; 20(12):2182-4

Coronavirus Genetically Redirected to the EGF Receptor Exhibits Effective Antitumor Activity against a Malignant Glioblastoma. J Virol. 2009; 83(15):7507-16

Retargeting of viruses to generate oncolytic agents. Verheije, M.H., Rottier, P.J. Adv Virol. 2012; 2012:798526. Review.

Coronavirus-host interactions in poultry
Coronaviruses are pathogens of both veterinary and human importance. The best known avian coronavirus is infectious bronchitis virus (IBV), which has a major impact on chicken health, and causes severe economical losses in the poultry industry. The current vaccines against IBV offer only limited protection, due to the circulation of many different serotypes. In addition, IBV-like strains are nowadays isolated from many other avian species, but their pathogenesis and host tropism is not well understood. Currently, we focus on the elucidation of avian coronavirus-host interactions at the molecular level, but also at the level of the animal by studying the pathogenesis of these viruses. Another part of this research line focuses on the interaction of avian coronaviruses with chicken innate immunity, in collaboration with other research groups within the Veterinary Faculty. Finally, we focus on the development of new vaccines against this important virus for poultry.

Key paper:
Binding of avian coronavirus spike proteins to host factors reflects virus tropism and pathogenicity. J.Virol. 2011; 85(17):8903-12

Contributions of the S2 spike ectodomain to attachment and host range of infectious bronchitis virus. Virus Res. 2013 Nov 6;177(2):127-37