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    Neuartige Polyomaviren in Menschen und nicht-humanen Primaten (2013)

    Art
    Hochschulschrift
    Autor
    Scuda, Nelly (WE 5)
    Quelle
    Berlin: Mensch und Buch Verlag, 2013 — VII, 167 Seiten
    ISBN: 978-3-86387-413-1
    Verweise
    URL (Volltext): http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000095998
    Kontakt
    Institut für Virologie

    Robert-von-Ostertag-Str. 7-13
    Gebäude 35
    14163 Berlin
    +49 30 838 51833
    viro@zedat.fu-berlin.de

    Abstract / Zusammenfassung

    Polyomaviruses are a family of small non-enveloped DNA viruses. They infect a wide range of birds and mammals and are able to cause severe diseases in immunocompromised individuals. Given the growing disease burden entailed by acquired immunodeficiencies, human PyVs are now increasingly considered emerging opportunistic pathogens.
    Gaining more insight into their diversity, prevalence, and etiopathogenesis is therefore essential. The present study assessed the following questions: (i) Are additional polyomaviruses circulating in humans and non-human primates? (ii) How is their phylogenetic relationship to other polyomaviruses? (iii) Are these viruses able to provide insight into possible transmission routes, tropisms and pathogenities? (iv) Is there evidence for the existence of so far unknown human polyomaviruses? A total of 792 necropsy samples of simian origin were analyzed for the presence of polyomaviruses by using degenerate primer-based PCR. With this approach a high prevalence of polyomaviruses in spleen, lymph node and intestine samples was detected and 30 novel non-human primate polyomaviruses were identified: 19 in great apes (15 in chimpanzees, three in gorillas and one in orangutan), five in Old World monkeys and six in New World monkeys. Seventeen complete genomes were amplified. Phylogenetic analysis revealed that these new polyomaviruses span nearly the entire known diversity of mammalian polyomaviruses. This fact suggests that primates as a whole, including humans, are infected with a plethora of polyomaviruses. Ten polyomaviruses detected in wild Great apes revealed a remarkably close relationship to the human MCPyV. Thus, MCPyV could be the result of interspecies transmission of a MCPyV-like chimpanzee polyomavirus to humans. Additional 597 human samples were tested by using a degenerate PCR, wherein urine samples proved as the most appropriate material for polyomavirus detection. An unknown polyomavirus sequence was amplified from the serum of a kidney transplant patient under immunosuppressive treatment. The genome of this virus was completely sequenced. In phylogenetic analyses, it appeared as the closest relative to the African green monkey-derived lymphotropic polyomavirus (LPyV).
    The reactivity of human sera against LPyV is due to crossreactivity between HPyV9 and LPyV. To further examine the diversity of human polyomaviruses we used a combinatorial approach comprised of initial degenerate primer-based PCR identification and phylogenetic analysis of non-human primate species. In addition, polyomavirus-specific serological analysis of human sera was applied. Four chimpanzee polyomaviruses with no human counterpart were expressed in E. coli for use as antigens in an ELISA. Human serum and plasma samples from both Côte d‘Ivoire and Germany showed frequent seropositivity for these four viruses. These results support the existence of additional polyomaviruses circulating within the human population that are genetically and serologically related to existing chimpanzee polyomaviruses. Given the accelerated rate of human polyomavirus discovery over the last few years, it appears very likely that further, still-unknown polyomaviruses are actually circulating in human populations. Elucidating the evolutionary development may foster a better understanding of the pathogenicity of the novel polyomaviruses.
    Therefore, our study on primates is of importance since it provides insight into polyomavirus diversity and tropism due to improved nucleic-based methods for the detection of unknown polyomaviruses.