Research Group 3: Wildlife diseases
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Research field: Virology

Head: Prof. Dr. Alex D. Greenwood

Research:

    1.   Historical Diseases and Hyperdiseases

 

 

    Taken from Figure 1 of Wyatt et al. PLoS One, 3(11) e3602

    While it is widely accepted that novel infectious disease can be a leading cause of serious population decline and even outright extinction in some invertebrate and vertebrate groups (e.g., amphibians) there are still no well-corroborated instances of such diseases having caused or significantly contributed to the complete collapse of species in mammals. Extinction by disease was proposed by MacPhee and Marx in 1997 as a possible cause of the end Pleistocene megafaunal mammal collapse. I am interested in using molecular methods to investigate ancient pathogens from relevant time periods such as the end Pleistocene. I am also interested in more recent extinction events and the contribution of disease to them.

    A case in point is the extinction of the endemic Christmas Island rat (Rattus macleari): although it has been argued that its disappearance ca. AD 1900 may have been partly or wholly caused by a pathogenic trypanosome carried by fleas hosted on recently-introduced black rats (Rattus rattus), no decisive evidence for this scenario has ever been provided. Using ancient DNA methods we have demonstrated that 1. Christmas Island rats were genetically distinct from invasive black rats 2. the two species did not hybridize and that putative hybrids described in the literature were morphological variants of R. rattus 3. rat infecting trypanosome sequence could be obtained from both invasive and endemic rats in two separate laboratories 4. endemic rat samples that pre-dated the arrival of black rats were trypanosome negative.

    This is the first molecular evidence for a pathogen emerging in a naïve mammal species immediately prior to its final collapse. We continue to investigate other species for co-occurrence of pathogens with population collapse.

    We have current project investigating similar declines and extinctions caused by viruses using archival samples in other mammalian groups including, Christmas Island pipistrelles, Carribean monk seals and African rodents

     

     

    References:

    MacPhee RDE, Marx PA (1997) The 40,000-year plague: Humans, hyperdisease, and first-contact extinctions. In: Goodman SM, Patterson BD editors. Natural change and human impact in Madagascar. Washington, DC: Smithsonian Institution Press. pp.169-217.

    Wyatt, K., Campos, P.F., Gilbert, M.T.P., Kolokotronis, S.O., Hynes, W., DeSalle, R., Daszak, P., MacPhee, R.D.E. and Greenwood A.D. (2008) Historical Mammal Extinction on Christmas Island (Indian Ocean) Correlates with Introduced Infectious Disease. PLoS One, 3(11) e3602

 

 

    2.   The process and consequences of retroviral endogenization

     

    Endogenous retroviruses or ERVs make up approximately 8% of the mammalian genomes. To keep things in perspective, classical genes that code for enzymes and structural proteins for example, make up only about 1.5 % of the genome. HERVs represent historical germline infections by exogenous retroviruses such as HIV, the virus that causes AIDS. They can expand in number within the genome by either re-infection of germ cells or by retrotransposition (a reverse transcription mediated copying mechanism) within germ cells. In some rodents, exogenous and endogenous retroviruses are hardly distinguishable in their overall behaviour and abilities to proliferate such as some murine leukemia viruses which can exist and exogenous and endogenous viruses.

    Research Focus 1: Changes in ERV expression in response to infectious agents.

    I am interested in how infectious agents interact with ERVs in terms of changing their normal behaviour and possibly contributing to disease. We have shown that infectious prions can alter ERV expression in mouse cell lines (Stengel et al. 2006a). Together with the German Primate Center in Göttingen, we are examing a changes in ERV expression as it relates to infection with prions responsible for Bovine Spongiform Encephalopathy (BSE). I am also interested in the interactions between exogenous and endogenous retroviruses and their expression. The analysis generally involves the use of endogeous retrovrirus specifc DNA microarrays (Seifarth et al. 2005, Stengel et al. 2006b)

    Research Focus 2: The process of retroviral endogenization.

     I am currently investigating the process of retroviral endogenization in real time using ancient DNA methods in collaboration with Dr. Al Roca of the University of Illinois, Urbana-Champaign (http://www.ansci.illinois.edu/directory/details.cfm?ID=3141). Also, to better understand the characteristics of retroviruses that endogenize, we are examining the distribution of complex endogenous retroviruses in under-investigated wildlife species.

    References:

    Seifarth, W., Frank, O., Zeilfelder, U., Spiess, B., Greenwood, A.D., Hehlmann, R., and Leib-Mösch, C. (2005) Comprehensive Analysis of Human Endogenous Retrovirus (HERV) Transcriptional Activity in Human Tissues with a Retrovirus-Specific Microarray. J. Virol, 79: 341-352.

    Stengel, A., Bach, C., Vorberg, I., Frank, O., Lutzny, G., Gilch, S., Erfle, Schätzl, H., Leib-Mösch, C., and Greenwood, A.D. (2006a) Prion infection influences murine endogenous retrovirus expression in neuronal cells. Biochem. Biophys. Res. Comm. 343 (3): 825-831

    Stengel, A., Roos, C., Hunsmann, G., Seifarth, W., Leib-Mösch, C. and Greenwood, A.D. (2006b) Expression profiles of endogenous retrovirus in Old World monkeys. J. Virol. 80 (9): 4415-4421.

     

     

    3.   Ancient Disease and its effects:

     

    Research Focus 1: Effects of diseases on extinct animals.

    I have worked extensively with woolly mammoth nuclear DNA for many years (Greenwood et al. 1999; Greenwood et al. 2001, Capelli et al. 2006, Roca et al. 2009). We are currently extending our prior woolly mammoth nuclear DNA studies to examine the population genetics of mammoths for loci relevant to recognition of foreign antigens and defense against pathogens.

    Research Focus 2: Identification of ancient microbes

    I am examining well preserved permafrost specimens for specific pathogens and commensall microbes to better understand the evolution of specific groups of DNA viruses.

    References:

    Greenwood, A.D., Capelli, C., Possnert, G., and Pääbo, S. (1999) Nuclear DNA sequences from late Pleistocene megafauna. Molecular Biology and Evolution 16(11): 1466-1473.

    Greenwood, A.D., Lee, F., Capelli, C., DeSalle, R., Tikhonov, A., Marx, P.A., and MacPhee, R.D.E. (2001) Evolution of endogenous retrovirus-like elements of the woolly mammoth (Mammuthus primigenius) and its relatives. Molecular Biology and Evolution 18(5): 840-847.

    Capelli, C., MacPhee, R.D.E., Roca, A., Brisighelli, F., Giorgiadis, N., O'Brien, S.J., and Greenwood, A.D. (2006) A nuclear DNA phylogeny of woolly mammoth (Mammuthus primigenius). Mol. Phyl. Evol. 40: 620-627.

    Roca AL, Ishida Y, Nikolaidis N, Kolokotronis SO, Fratpietro S, Stewardson K, Hensley S, Tisdale M, Boeskorov G, Greenwood AD. (2009) Genetic variation at hair length candidate genes in elephants and the extinct woolly mammoth. BMC Evol Biol. 9(1):232