Manuela Rehtanz

University of Louisville, Louisville, Kentucky, United States

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Publications (10)26.24 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The number of studies addressing neoplasia in marine mammals has recently increased, giving rise to concern whether such lesions could be reflective of an emerging infectious disease. Eight species-specific viruses, seven papillomaviruses (PVs) and two herpesviruses (HVs) have separately been shown to be associated with genital tumors in Atlantic bottlenose dolphins (Tursiops truncatus, Tt): TtPV1-6, as well as HVs provisionally assigned the names DeHV4 and -5 (Delphinid HVs). A definite causal role of these viruses in cell transformation remains to be demonstrated. Concurrent PV- and HV-infection has never been reported in marine mammals. DNA extractions from biopsies of genital tumors derived from 15 free-ranging Atlantic bottlenose dolphins were selected for molecular examination. Polymerase chain reaction (PCR) analyses revealed the presence of DeHV4, while a serological screening using an antibody-based TtPV enzyme-linked immunosorbent assay (ELISA) demonstrated previous and/or current infection of the HV-positive dolphins with at least one TtPV type. Therefore, care must be taken when drawing conclusions about viral causalities in tumor development, since the "hit and run" and other mechanisms have been described for types of both viral families. This study presents the first evidence of marine mammals having a history of PV- as well as HV-infection and discusses the disputed effects of viral co-infection.
    Veterinary Microbiology 06/2012; · 3.13 Impact Factor
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    ABSTRACT: In 1997, cutaneous papillomatosis caused by Florida manatee (Trichechus manatus latirostris [Tm]) papillomavirus 1 (TmPV1) was detected in seven captive manatees at the Homosassa Springs Wildlife State Park, Florida, USA, and, subsequently, in two wild manatees from the adjacent Homosassa River. Since then, papillomatosis has been reported in captive manatees housed in other locations, but not in wild animals. To determine TmPV1 antibody prevalence in captive and wild manatees sampled at various locations throughout Florida coastal regions, virus-like particles, composed of the L1 capsid protein of TmPV1, were generated with a baculovirus expression system and used to measure anti-TmPV1 antibodies in an enzyme-linked immunosorbent assay. Serologic analysis of 156 manatees revealed a TmPV1 antibody prevalence of 26.3%, with no significant difference between captive (n=39) and wild (n=117) manatees (28.2% and 25.6%, respectively). No antibody-positive wild animal showed PV-induced cutaneous lesions, whereas papillomatosis was observed in 72.7% of antibody-positive captive manatees. Our data indicate that Florida manatees living in the wild are naturally infected by TmPV1 but rarely show TmPV1-induced papillomatosis. Hence, it appears that the wild population would not be harmed in a case of contact with captive animals without visible lesions and productive infections, which could be thus released into the wild.
    Journal of wildlife diseases 07/2011; 47(3):673-84. · 1.27 Impact Factor
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    ABSTRACT: Genital epithelial tumors of Atlantic bottlenose dolphins (Tursiops truncatus [Tt]) and Burmeister's porpoises (Phocoena spinipinnis) were formerly shown to be associated with papillomavirus (PV) infection. Papillomaviruses are highly prevalent viruses involved in the development of various tumor types in a wide range of animals, and so-called high-risk PVs contribute to malignant progression. In marine mammals, the incidence and prevalence of PV infection, transmission pathways, and persistence of infection are largely unknown. Using virus-like particles of bottlenose dolphin PV type 1 (TtPV1) as the antigen, enzyme-linked immunosorbent assay (ELISA) studies were conducted to evaluate PV antibody prevalence in bottlenose dolphins. In total, sera obtained from 115 dolphins were examined. Fifty-one percent of captive dolphins (n=18 of 35) and 90% of free-ranging dolphins (n=72 of 80) were antibody positive. Higher ELISA reactivity was observed among males compared with females. Sexually immature dolphins appeared more likely to seroconvert with age. Besides determining their PV antibody prevalence, each animal was also assessed for the presence of orogenital tumors. Interestingly, the mean age of free-ranging dolphins with tumors (n=21) was 11.2 yr compared with 29.9 yr in captive dolphins with tumors (n=9). Results from the current study suggest PV infection in bottlenose dolphins is common, that the main route of PV transmission among them may be horizontal, and that orogenital neoplasia may develop in early life stages of certain free-ranging bottlenose dolphins.
    Journal of wildlife diseases 01/2010; 46(1):136-45. · 1.27 Impact Factor
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    ABSTRACT: Papillomaviruses (PVs) have been shown as being the etiologic agents of various benign and malignant tumours in many vertebrate species. In dolphins and porpoises, a high prevalence of orogenital tumours has recently been documented with at least four distinct novel species-specific PV types detected in such lesions. Therefore, we generated the immunological reagents to establish a serological screening test to determine the prevalence of PV infection in Atlantic bottlenose dolphins [(Tursiops truncatus (Tt)]. Using the baculovirus expression system, virus-like particles (VLPs) derived from the L1 proteins of two TtPV types, TtPV1 and TtPV2, were generated. Polyclonal antibodies against TtPV VLPs were produced in rabbits and their specificity for the VLPs was confirmed. Electron microscopy and enzyme-linked immunosorbent assay (ELISA) studies revealed that the generated VLPs self-assembled into particles presenting conformational immunodominant epitopes. As such, these particles are potential antigen candidates for a TtPV vaccine. Subsequently, the VLPs served as antigens in initial ELISA tests using sera from six bottlenose dolphins to investigate PV antibody presence. Three of these sera were derived from dolphins with genital tumour history and showed positive PV ELISA reactivity, while the remaining sera from lesion-free dolphins were PV antibody-negative. The results suggest that the developed screening test may serve as a potential tool for determining PV prevalence and thus for observing transmission rates in dolphin populations as the significance of PV infection in cetaceans starts to unfold.
    Veterinary Microbiology 08/2008; 133(1-2):43-53. · 3.13 Impact Factor
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    ABSTRACT: Phylogenetic analysis of novel dolphin (Tursiops truncatus) papillomavirus sequences, TtPV1, -2, and -3, indicates that the early and late protein coding regions of their genomes differ in evolutionary history. Sliding window bootscan analysis showed a significant a change in phylogenetic clustering, in which the grouped sequences of TtPV1 and -3 move from a cluster with the Phocoena spinipinnis PsPV1 in the early region to a cluster with TtPV2 in the late region. This provides indications for a possible recombination event near the end of E2/beginning of L2. A second possible recombination site could be located near the end of L1, in the upstream regulatory region. Selection analysis by using maximum likelihood models of codon substitutions ruled out the possibility of intense selective pressure, acting asymmetrically on the viral genomes, as an alternative explanation for the observed difference in evolutionary history between the early and late genomic regions of these cetacean papillomaviruses.
    Virology 08/2008; · 3.37 Impact Factor
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    ABSTRACT: Antibodies in the sera of patients with lacaziosis recognized an approximately 193-kDa antigen and other Lacazia loboi antigens. Paracoccidioides brasiliensis gp43 antigen was detected by all evaluated sera, but they failed to detect a protein with the same molecular mass in L. loboi extracts. This study is the first to examine the humoral response to L. loboi antigens by using multiple host sera.
    Clinical and vaccine Immunology: CVI 02/2008; 15(1):164-7. · 2.60 Impact Factor
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    ABSTRACT: A novel papillomavirus (PV) was isolated from a genital condyloma of a free-ranging bottlenose dolphin inhabiting the coastal waters of Charleston Harbor, SC, USA: Tursiops truncatus papillomavirus type 2 (TtPV2). This novel virus represents the first isolated North American cetacean PV and the first American bottlenose dolphin PV. After the viral genome was cloned, sequenced and characterized genetically, phylogenetic analyses revealed that TtPV2 is most similar to the only published cetacean PV isolated and characterized thus far, Phocoena spinipinnis PV type 1 (PsPV1). A striking feature of the genome of TtPV2, as well as that of PsPV1, is the lack of an E7 open reading frame, which typically encodes one of the oncogenic proteins believed to be responsible for malignant transformation in the high-risk mucosotropic human papillomaviruses (HPVs). TtPV2 E6 contains a PDZ-binding motif that has been shown to be involved in transformation in the case of high-risk genital HPVs.
    Journal of General Virology 01/2007; 87(Pt 12):3559-65. · 3.13 Impact Factor
  • Aquatic Mammals 01/2005; 31(4):473-480. · 0.70 Impact Factor
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    ABSTRACT: Using a yeast two-hybrid screen, we identified human nucleosome assembly protein 1 (hNAP-1) as a protein interacting with the activation domain of the transcriptional activator encoded by papillomaviruses (PVs), the E2 protein. We show that the interaction between E2 and hNAP-1 is direct and not merely mediated by the transcriptional coactivator p300, which is bound by both proteins. Coexpression of hNAP-1 strongly enhances activation by E2, indicating a functional interaction as well. E2 binds to at least two separate domains within hNAP-1, one within the C terminus and an internal domain. The binding of E2 to hNAP-1 is necessary for cooperativity between the factors. Moreover, the N-terminal 91 amino acids are crucial for the transcriptional activity of hNAP-1, since deletion mutants lacking this N-terminal portion fail to cooperate with E2. We provide evidence that hNAP-1, E2, and p300 can form a ternary complex efficient in the activation of transcription. We also show that p53 directly interacts with hNAP-1, indicating that transcriptional activators in addition to PV E2 interact with hNAP-1. These results suggest that the binding of sequence-specific DNA binding proteins to hNAP-1 may be an important step contributing to the activation of transcription.
    Molecular and Cellular Biology 04/2004; 24(5):2153-68. · 5.04 Impact Factor
  • G Steger, M Rehtanz, C Schnabel
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    ABSTRACT: The expression of the oncogenes E6 and E7 of the cervical cancer associated human papillomavirus type 18 was shown to be directed from the promoter in position 105 (P105), which is reportedly the only early promoter located within the long control region (LCR). However, in C33A cells transiently transfected with a reporter construct containing the LCR of HPV18 in front of the luciferase gene a transcript initiating at position 56 was present in addition to those initiating from the P105. A perfect TATA Box consensus sequence 30 bp further upstream, which is highly conserved among HPVs associated with cervical cancer, was required for the activity of this novel promoter, denoted here as P56. The P56 specific transcript obviously depends on promoter downstream sequences, since transcripts initiating from the P56 were not present when the CAT gene was cloned downstream of the LCR. We detected transcripts initiating from both the P105 and the P56 in primary keratinocytes harboring episomal HPV18 as well as in the HPV 18 positive cervical carcinoma cell lines HeLa, C4-1 and SW756. Our data suggest that in HPV18, the expression of the early viral proteins including the oncogenes might be directed from a second promoter, located within the LCR.
    Archives of Virology 02/2001; 146(11):2069-84. · 2.28 Impact Factor

Publication Stats

108 Citations
26.24 Total Impact Points

Institutions

  • 2012
    • University of Louisville
      Louisville, Kentucky, United States
  • 2004
    • University of Cologne
      • Institute of Virology
      Köln, North Rhine-Westphalia, Germany