Volume 1

The revision of the EU Directive on the protection of animals used for scientific purposes / House of Lords. European Union Committee.

  • Great Britain. Parliament. House of Lords. European Union Committee
Date:
2009
Catalogue details

Licence: Open Government Licence

Credit: The revision of the EU Directive on the protection of animals used for scientific purposes / House of Lords. European Union Committee. Source: Wellcome Collection.

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    I REFERENCE 1. Rieder E, Berinstein A, Baxt B, Kang A, Mason P W (1996) Propagation of an attenuated virus by design: engineering a novel receptor for a noninfectious foot-and-mouth disease virus. Proc Natl Acad Sci USA 93:10428-10433. B2. Hepatitis C: Three-dimensional in vitro liver models The Dr Hadwen Trust is currently funding Dr Brian Thomson, a Clinical Associate Professor in the School of Molecular Medical Sciences at Nottingham University, to use tissue engineering to develop three- dimensional in vitro models of human liver. These will permit both the long-term growth and preservation of function of primary human hepatocytes in vitro. The 3-D spheroids will also include hepatic stellate cells which play a key role in liver response to injury. The inclusion of these cells provides an excellent basis for modelling human liver disease. Building on his earlier work based on rodent cells [1], Dr Thomson is adapting the approach to develop a 3- D human hepatocyte culture for research into human hepatitis viruses. Hepatitis B is currently researched in animals including chimpanzees, and hepatitis C studies still use chimpanzees, tamarins and marmosets [2, 3]. The development of a robust, multicellular culture system which supports viral replication and virion production will enable the replacement of primates and small mammals in many areas of hepatitis virus research including: determination of infectivity for virus and molecular clones; studies of viral kinetics; studies of cytopathicity; and neutralisation studies. REFERENCES 1. Thomas R J, Bennett A, Thomson B, Shakesheff K M (2006) Hepatic stellate cells on poly(DL-lactic acid) surfaces control the formation of 3D hepatocyte co-culture aggregates in vitro. Eur Cell Mater 11:16—26 2. Dandri M, Volz T K, Lutgehetmann M & Petersen. Animal models for the study of HBV replications and its variants. J Clin Virology 2005, 34 Suppl 1: 54-62. 3. Grakoui A, Hanson H L and Rice C M. Bad time for Bonzo? Experimental models of hepatitis C virus infection, replication and pathogenesis. Hepatology 2001, 33: 489-495. B3. Viral encephalitis: Development of a human ex-vivo blood brain barrier model for research As a medical research charity, we are currently funding Professor Tom Solomon, at Liverpool University in England, to establish a robust, working ex vivo model of the human blood brain barrier (BBB) to examine the putative mechanisms of viral entry into the nervous system. Currently studies of the pathogenesis of viral encephalitis are very dependent on animal models, including primates. For example, a study of Japanese encephalitis virus using 20 rhesus monkeys inoculated by intranasal virus caused animals to suffer depression, anorexia, tremors, paralysis, coma and death [1]. The Liverpool Brain Infections Group is one of the leading international groups studying viral encephalitis in humans, examining the pathogenesis during disease, and also in human post-mortem material [2-5]. Having established a robust, working ex-vivo model of the human BBB for examining mechanisms of viral entry into the nervous system, the second phase of Professor Solomon’s research will focus on Japanese encephalitis virus (JEV), one of the most important causes of viral encephalitis globally. The roles of virus replication and the pro-inflammatory cytokine response on BBB integrity will be explored. Professor Solomon will also test the hypothesis that the pro-inflammatory cytokine milieu induced by JEV replication is more important in disrupting the BBB than viral replication itself. The longer term objectives are to be able to study treatments for encephalitis in this model system, which will be an important step towards new therapies. Targeted European support for this kind of research could have an enormous impact on progress in understanding and treating viral encephalitis, whilst sparing some primates from suffering. REFERENCES 1. Raengsakulrach B, Nisalak A, Gettayacamin M, et al (1999) Safety, immunogenicity, and protective efficacy of NYVAC-JEV and ALVAC-JEV recombinant Japanese encephalitis vaccines in rhesus monkeys. Am J Trop Med Hyg 60:343-9, 2. Solomon T. (2004). Current Concepts—Flavivirus encephalitis. N Engl J Med 351: 370-8.