Morbilluvirus
Morbilliviruses are an antigenically related group of viruses in the family Paramyxoviridae. The type virus of the group is human Measles Virus (MV) but it also includes important animal pathogens such as Rinderpest Virus (RPV) of cattle, buffalo and wild bovids, Peste des Petits ruminants (PPR) virus, which infects mainly sheep and goats, Canine Distemper Virus (CDV) of domestic dogs and wild carnivore species, Phocine Distemper Virus (PDV) of seals and two viruses isolated from cetacean species, Dolphin morbillivirus (DMV) and Porpoise Morbillivirus (PMV).
Morbilliviruses are highly pathogenic in their hosts and the economic consequences of epizootics of rinderpest and PPR can be devastating. PPR infection is one of the most important constraints to the increased production of small ruminants in West Africa and recently severe epizootics have occurred in the Middle East and across the north of the Indian sub-continent. Rinderpest continues to pose a serious threat to cattle, buffalo and wild ruminants in parts of eastern Africa but a global eradication campaign is in place with the aim of achieving eradication of the disease by 2010. The group is actively involved in this project by helping to develop new marker vaccines and their associated serological tests and by providing scientific advice and training. A severe outbreak of PDV occurred in Northern Europe in 2002, resulting in the deaths of many seals.
The group’s research interests can be divided into three main areas:
Epidemiology
Molecular techniques have been applied to the diagnosis of the different morbilliviruses and RT-PCR assays are available which can distinguish the different viruses in clinical and post-mortem tissues. Sequencing studies have shown that, despite being only one serotype of each virus, there are different genetic lineages of each virus and this allows tracing of disease outbreaks outside their known geographic area.
Vaccinology
In the field of vaccine development the group has produced both vaccinia and capripox recombinant vaccines to protect against rinderpest and PPR. The capripox recombinants act as dual vaccines, for example the PPR recombinant protects against sheep and goat pox as well as PPR infections. Currently we are developing new marker vaccines for rinderpest using reverse genetics technology.
Pathogenesis
The development of reverse genetics for negative-strand RNA viruses in 1994 made it possible to study the effects of specific genome changes on the nature of the virus phenotype, both in vitro and in the host animal. Revere genetics for RPV was developed in 1996 when a complete copy of the RBOK vaccine strain was rescued from cDNA. Subsequently the virulent parent of the vaccine strain was rescued for cDNA and shown to retain its virulence for cattle. It was then possible to demonstrate that the vaccine, which is safe and highly efficacious, had multiple gene mutations that explained its high attenuation and stability. In addition we were able to show that the extragenic promoter regions also had played a role in determining the pathogenic nature of the virus.
Reference list
- Baron, M.D. and Barrett, T. (1997) Rescue of recombinant rinderpest virus from cloned cDNA. Journal of Virology, 71, 1265-1271 [Full text].
- Baron, M.D. and Barrett, T. (2000) Rinderpest viruses lacking the C and V proteins show specific defects in growth and transcription of viral RNAs. Journal of Virology, 74, 2603-2611 [Full text].
- Dhar, P., Sreenivasa, B.P., Barrett, T., Corteyn, M., Singh, R.P., and Bandyopadhyay, S.K.(2002) Recent Epidemiology of Peste des Petits Ruminants Virus (PPRV). Veterinary Microbiology, 88, 153-159 [Full text].
- Das, S.C., Baron, M.D. and Barrett, T. (2000) Recovery and characterisation of a chimeric rinderpest virus with the glycoproteins of peste des petits ruminants virus: Homologous F and H proteins are required for virus viability. Journal of Virology, 74, 9039-9047 [Full text].
- Heaney, J., Barrett, T. and Cosby, L. (2002) Inhibition of leucocyte proliferation by morbilliviruses. Journal of Virology, 76, 3579-3584 [Full text].
- Kennedy, S., Kuiken, T., Jepson, P.D., Deaville, R., Forsyth, M., Barrett, T., van de Bildt, M.W.G, Eybatov, T., Duck, C., Kydyrmano, A., Mitrofanov, I., A.D.M.E. Osterhaus & Wilson, S. (2000) Mass die-Off of Caspian seals caused by canine distemper virus. Emerging Infectious Diseases, 6, 637-639 [Full text].
- Lund, B., Tiwari, A., Galbraith, S., Baron, M.D., Morrison, W.I. and Barrett, T. (2000) Vaccination of cattle with attenuated rinderpest virus stimulates CD4+ T cell responses with a broad viral antigen specificity and does not induce detectable immunosuppression. Journal of General Virology, 81, 2137-2146 [Full text].
- Ngichabe, C.K., Wamwayi, H.M, Ndungu1, E.K., Mirangi1, P.K., Bostock, C.J., Black, D.N. and Barrett, T. (2002) Long Term Immunity in African Cattle Vaccinated with a Recombinant Capripox-Rinderpest virus Vaccine. Epidemiology and Infection, 128, 343-349 [Abstract].
- Ohishi, K., Inui, K., Barrett, T. and Yamanouchi, K. (2000) Long-term protective immunity to rinderepst in cattle following a single vaccination with a recombinant vaccinia virus expressing the virus haemagglutinin protein. Journal of General Virology 81, 1439-1446 [Full text].
- Ohishi, K., Inui, K., Yamanouchi, K and Barrett, T. (1999) Cell-mediated immune responses in cattle vaccinated with a vaccinia virus recombinant expressing the nucleocapsid protein of rinderpest virus. Journal of General Virology, 80, 1627-1634 [Full text].
- Ozkul, A., Akca, Y., Alkan, F., Barrett, T., Taner, K., Dagalp, S.B., Anderson, J., Yesilbag, K., Cokcaliskan, C., Gencay, A. and Burgu, I. (2002) Prevalance, distribution and host range of peste des petits ruminants virus in Turkey, Emerging Infectious Diseases, 8, 708-712 [Full text].
- Van Bressem, M-F., Van Waerebeek, K., Jepson, P., Raga, J.A., DI Beneditto, A. P., Siciliano, S., Ramos, R., Kant, W., Peddemors, V., Kinoshita, R., Ross, P. S., López-Fernandez, A., Evans, K., Crespo, E. and Barrett, T. (2001). An insight into the epidemiology of dolphin morbillivirus worldwide. Veterinary Microbiology, 287-304 [Full text].
- Walsh, E.P., Baron, M.D., Rennie, L., Monahan, P., Anderson, J. and Barrett, T. (2000) Recombinant rinderpest vaccines expressing membrane anchored proteins as genetic markers: evidence for exclusion of marker protein from the virus envelope. Journal of Virology, 74, 10165-10175 [Full text].
Books
Anderson, J., Barrett, T. and Scott, G.R. (1996) Manual on the diagnosis of rinderpest. Second edition, FAO Rome.
Book Chapters- Barrett, T. and Rossiter, P. (1999) Rinderpest: the disease and its impact on humans and animals. Advances in virus research, 53, 89-110.
- Barrett T (2001) Morbilliviruses: dangers old and new. In " New challenges to health:the threat of virus infection". Society for General Microbiology, Symposium 60. Eds. G.L. Smith, J.W. Mc Cauley and D.J. Rowlands, pp155-178. Cambridge University Press.
- Barrett, T. and Rima, B.K. (2002). The Morbilliviruses. In "The Springer Index of Viruses. Eds. C.A. Tidona and G. Darai, pp 645-650. Springer, Berlin.
- Barrett, T. and Rima, B.K. (2002) Molecular Biology of Morbillivirus Diseases of Marine Mammals. In "Molecular and Cell Biology of Marine Mammals", Ed. Carl J. Pfeiffer, pp161-172. Krieger Publishing Company, Florida.
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'Dardanidae duri, quae uos a stirpe parentum
prima tulit tellus, eadem uos ubere laeto
accipiet reduces. Antiquam exquirite matrem:
hic domus Aeneae cunctis dominabitur oris,
et nati natorum, et qui nascentur ab illis.'
We can easily forgive a child who is afraid of the dark; the real tragedy of life is when men are afraid of the light.
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