The Experts below are selected from a list of 1224 Experts worldwide ranked by ideXlab platform
Nicole Fischer - One of the best experts on this subject based on the ideXlab platform.
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In-Depth Investigation of Archival and Prospectively Collected Samples Reveals No Evidence for XMRV Infection in Prostate Cancer
2016Co-Authors: Deanna Lee, Nicole Fischer, Jaydip Das Gupta, Xiaoxing Qiu, Christina Gaughan, Imke Steffen, Ning Tang, Ka-cheung Luk, Anatoly Urisman, Ross MolinaroAbstract:XMRV, or xenotropic murine leukemia virus (MLV)-related virus, is a novel Gammaretrovirus originally identified in studies that analyzed tissue from prostate cancer patients in 2006 and blood from patients with chronic fatigue syndrome (CFS) in 2009. However, a large number of subsequent studies failed to confirm a link between XMRV infection and CFS or prostate cancer. On the contrary, recent evidence indicates that XMRV is a contaminant originating from the recombination of two mouse endogenous retroviruses during passaging of a prostate tumor xenograft (CWR22) in mice, generating laboratory-derived cell lines that are XMRV-infected. To confirm or refute an association between XMRV and prostate cancer, we analyzed prostate cancer tissues and plasma from a prospectively collected cohort of 39 patients as well as archival RNA an
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apobec 3g efficiently reduces infectivity of the human exogenous Gammaretrovirus xmrv
PLOS ONE, 2010Co-Authors: Kristin Stieler, Nicole FischerAbstract:Background The human exogenous Gammaretrovirus XMRV is thought to be implicated in prostate cancer and chronic fatigue syndrome. Besides pressing epidemiologic questions, the elucidation of the tissue and cell tropism of the virus, as well as its sensitivity to retroviral restriction factors is of fundamental importance. The Apobec3 (A3) proteins, a family of cytidine deaminases, are one important group of host proteins that control primary infection and efficient viral spread. Methodology/Principal Findings Here we demonstrate that XMRV is resistant to human Apobec 3B, 3C and 3F, while being highly susceptible to the human A3G protein, a factor which is known to confer antiviral activity against most retroviruses. We show that XMRV as well as MoMLV virions package Apobec proteins independent of their specific restriction activity. hA3G was found to be a potent inhibitor of XMRV as well as of MoMLV infectivity. In contrast to MoMLV, XMRV infection can also be partially reduced by low concentrations of mA3. Interestingly, established prostate cancer cell lines, which are highly susceptible to XMRV infection, do not or only weakly express hA3G. Conclusions Our findings confirm and extend recently published data that show restriction of XMRV infection by hA3G. The results will be of value to explore which cells are infected with XMRV and efficiently support viral spread in vivo. Furthermore, the observation that XMRV infection can be reduced by mA3 is of interest with regard to the current natural reservoir of XMRV infection.
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xenotropic murine leukemia virus related Gammaretrovirus in respiratory tract
Emerging Infectious Diseases, 2010Co-Authors: Nicole Fischer, Kristin Stieler, Claudia Schulz, Christoph Lange, Oliver Höhn, Christian Drosten, Martin AepfelbacherAbstract:Xenotropic murine leukemia virus–related Gammaretrovirus (XMRV) has been recently associated with prostate cancer and chronic fatigue syndrome. To identify nucleic acid sequences, we examined respiratory secretions by using PCR. XMRV-specific sequences were detected in 2%–3% of samples from 168 immunocompetent carriers and ≈10% of samples from 161 immunocompromised patients.
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prevalence of human Gammaretrovirus xmrv in sporadic prostate cancer
Journal of Clinical Virology, 2008Co-Authors: Nicole Fischer, Claudia Schulz, Martin Aepfelbacher, Olaf J C Hellwinkel, Felix K H Chun, Hartwig Huland, Thorsten SchlommAbstract:Abstract Background We previously identified a novel exogenous Gammaretrovirus (xenotropic murine leukemia virus-related Gammaretrovirus (XMRV)) using a pan-viral microarray. XMRV is the first MLV-related virus found in human infection. Forty percent (8/20) of familial prostate cancer patients homozygous for a mutation in RNase L (R462Q) were positive for XMRV, while the virus was rarely (1/66) detected in familial prostate cancer patients heterozygous for R462Q or carrying the wild type allele. Objectives To determine the presence of XMRV in non-familial prostate cancer samples. Study design RNA from prostate tissue was analyzed for XMRV using nested RT-PCR. In all samples, RNase L (R462Q) genotyping was performed using an allele-specific PCR. Results XMRV-specific sequences were detected in one of 105 tissue samples from non-familial prostate cancer patients and from one of 70 tissue samples from men without prostate cancer. The two XMRV-positive patients were wild type or heterozygous for the R462Q mutation and thus carried at least one fully functional RNase L allele. Conclusions XMRV was rarely detected in non-familial prostate cancer samples from Northern European patients. The homozygous mutation R462Q (QQ) was significantly underrepresented (
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identification of a novel Gammaretrovirus in prostate tumors of patients homozygous for r462q rnasel variant
PLOS Pathogens, 2006Co-Authors: Anatoly Urisman, Nicole Fischer, Ross J Molinaro, Eric A Klein, Sarah J Plummer, Graham Casey, Krishnamurthy Malathi, Cristina Magigalluzzi, Raymond R TubbsAbstract:Ribonuclease L (RNase L) is an important effector of the innate antiviral response. Mutations or variants that impair function of RNase L, particularly R462Q, have been proposed as susceptibility factors for prostate cancer. Given the role of this gene in viral defense, we sought to explore the possibility that a viral infection might contribute to prostate cancer in individuals harboring the R462Q variant. A viral detection DNA microarray composed of oligonucleotides corresponding to the most conserved sequences of all known viruses identified the presence of gammaretroviral sequences in cDNA samples from seven of 11 R462Q-homozygous (QQ) cases, and in one of eight heterozygous (RQ) and homozygous wild-type (RR) cases. An expanded survey of 86 tumors by specific RT-PCR detected the virus in eight of 20 QQ cases (40%), compared with only one sample (1.5%) among 66 RQ and RR cases. The full-length viral genome was cloned and sequenced independently from three positive QQ cases. The virus, named XMRV, is closely related to xenotropic murine leukemia viruses (MuLVs), but its sequence is clearly distinct from all known members of this group. Comparison of gag and pol sequences from different tumor isolates suggested infection with the same virus in all cases, yet sequence variation was consistent with the infections being independently acquired. Analysis of prostate tissues from XMRV-positive cases by in situ hybridization and immunohistochemistry showed that XMRV nucleic acid and protein can be detected in about 1% of stromal cells, predominantly fibroblasts and hematopoietic elements in regions adjacent to the carcinoma. These data provide to our knowledge the first demonstration that xenotropic MuLV-related viruses can produce an authentic human infection, and strongly implicate RNase L activity in the prevention or clearance of infection in vivo. These findings also raise questions about the possible relationship between exogenous infection and cancer development in genetically susceptible individuals.
Joachim Denner - One of the best experts on this subject based on the ideXlab platform.
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immunisation with the membrane proximal external region of gp41 of hiv 1 grafted into the transmembrane envelope protein of a Gammaretrovirus
Retrovirology, 2012Co-Authors: N Strasz, V A Morozov, J Kreutzberger, M Lau, Joachim DennerAbstract:Background Immunisation with the transmembrane envelope (TM) proteins p15E of different Gammaretroviruses (e.g., porcine endogenous retrovirus, feline leukaemia virus, Koala retrovirus) resulted in strong neutralising activity, the antibodies recognised epitopes in the fusion peptide proximal region (FPPR) and in the membrane proximal external region (MPER). The MPER epitopes were localised similarly as the epitopes recognised by the broadly neutralising antibodies 2F5 and 4E10 in gp41 of HIV-1. Despite the evolutionary difference between HIV-1 and the Gammaretroviruses, the MPER epitope of antibodies neutralising PERV (FEGWFN) showed partial homology to the epitope of the 4E10 (NWFNIT, note three identical amino acids). To generate hybrid antigens able to induce 2F5/4E10-like antibodies, sequences of the MPER and FPPR of gp41 were grafted into the p15E backbone of a Gammaretrovirus.
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detection of a Gammaretrovirus xmrv in the human population open questions and implications for xenotransplantation
Retrovirology, 2010Co-Authors: Joachim DennerAbstract:XMRV (xenotropic murine leukaemia virus-related virus) is a Gammaretrovirus that has been detected in human patients with prostate carcinoma, chronic fatigue syndrome (CFS) and also in a small percentage of clinically healthy individuals. It is not yet clear whether the distribution of this virus is primarily limited to the USA or whether it is causally associated with human disease. If future investigations confirm a broad distribution of XMRV and its association with disease, this would have an impact on xenotransplantation of porcine tissues and organs. Xenotransplantation is currently being developed to compensate for the increasing shortage of human material for the treatment of tissue and organ failure but could result in the transmission of porcine pathogens. Maintenance of pathogen-free donor animals will dramatically reduce this risk, but some of the porcine endogenous retroviruses (PERVs) found in the genome of all pigs, can produce infectious virus and infect cultured human cells. PERVs are closely related to XMRV so it is critical to develop tests that discriminate between them. Since recombination can occur between viruses, and recombinants can exhibit synergism, recipients should be tested for XMRV before xenotransplantation.
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lack of evidence for xenotropic murine leukemia virus related virus xmrv in german prostate cancer patients
Retrovirology, 2009Co-Authors: Oliver Höhn, Pia Barbarotto, Lars Niederstadt, Nadine Beimforde, Hans Krause, Kurt Miller, Reinhard Kurth, Joachim Denner, Norbert BannertAbstract:Background A novel Gammaretrovirus named xenotropic murine leukemia virus-related virus (XMRV) has been recently identified and found to have a prevalence of 40% in prostate tumor samples from American patients carrying a homozygous R462Q mutation in the RNaseL gene. This mutation impairs the function of the innate antiviral type I interferon pathway and is a known susceptibility factor for prostate cancer. Here, we attempt to measure the prevalence of XMRV in prostate cancer cases in Germany and determine whether an analogous association with the R462Q polymorphism exists.
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transspecies transmission of the endogenous koala retrovirus
Journal of Virology, 2006Co-Authors: Uwe Fiebig, Reinhard Kurth, Norbert Bannert, Manuel Garcia Hartmann, Joachim DennerAbstract:The koala retrovirus (KoRV) is a Gammaretrovirus closely related to the gibbon ape leukemia virus and induces leukemias and immune deficiencies associated with opportunistic infections, such as chlamydiosis. Here we characterize a KoRV newly isolated from an animal in a German zoo and show infection of human and rat cell lines in vitro and of rats in vivo, using immunological and PCR methods for virus detection. The KoRV transmembrane envelope protein (p15E) was cloned and expressed, and p15E-specific neutralizing antibodies able to prevent virus infection in vitro were developed. Finally, evidence for immunosuppressive properties of the KoRV was obtained.
Martin Aepfelbacher - One of the best experts on this subject based on the ideXlab platform.
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xenotropic murine leukemia virus related Gammaretrovirus in respiratory tract
Emerging Infectious Diseases, 2010Co-Authors: Nicole Fischer, Kristin Stieler, Claudia Schulz, Christoph Lange, Oliver Höhn, Christian Drosten, Martin AepfelbacherAbstract:Xenotropic murine leukemia virus–related Gammaretrovirus (XMRV) has been recently associated with prostate cancer and chronic fatigue syndrome. To identify nucleic acid sequences, we examined respiratory secretions by using PCR. XMRV-specific sequences were detected in 2%–3% of samples from 168 immunocompetent carriers and ≈10% of samples from 161 immunocompromised patients.
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Host range and cellular tropism of the human exogenous Gammaretrovirus XMRV
Virology, 2010Co-Authors: Kristin Stieler, Martin Aepfelbacher, C. Schulz, M. Lavanya, C. Stocking, N. FischerAbstract:Recently, the first human infection with an exogenous Gammaretrovirus (XMRV) was reported. In its initial description, XMRV was confined to prostate stromal fibroblasts, although subsequent reports demonstrated XMRV protein expression in prostate epithelial cells. Most recently, XMRV has been detected in blood cells of patients with chronic fatigue syndrome. The aim of this study was to elucidate the transmission routes and tissue tropism of XMRV by comparing its host range, receptor usage and LTR functionality with other MLV isolates. We demonstrate using pseudotype experiments that XMRV Env mediates efficient infection of cells from different species. We show that replication competent XMRV infects various human cell types, including hematopoietic cell lines and prostate stromal fibroblasts. XMRV-LTR activity is significantly higher in the prostate cancer cell line LNCaP and in prostate stromal fibroblasts, compared to other cell types tested and could be one factor contributing to efficient viral spread in prostate tissue.
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prevalence of human Gammaretrovirus xmrv in sporadic prostate cancer
Journal of Clinical Virology, 2008Co-Authors: Nicole Fischer, Claudia Schulz, Martin Aepfelbacher, Olaf J C Hellwinkel, Felix K H Chun, Hartwig Huland, Thorsten SchlommAbstract:Abstract Background We previously identified a novel exogenous Gammaretrovirus (xenotropic murine leukemia virus-related Gammaretrovirus (XMRV)) using a pan-viral microarray. XMRV is the first MLV-related virus found in human infection. Forty percent (8/20) of familial prostate cancer patients homozygous for a mutation in RNase L (R462Q) were positive for XMRV, while the virus was rarely (1/66) detected in familial prostate cancer patients heterozygous for R462Q or carrying the wild type allele. Objectives To determine the presence of XMRV in non-familial prostate cancer samples. Study design RNA from prostate tissue was analyzed for XMRV using nested RT-PCR. In all samples, RNase L (R462Q) genotyping was performed using an allele-specific PCR. Results XMRV-specific sequences were detected in one of 105 tissue samples from non-familial prostate cancer patients and from one of 70 tissue samples from men without prostate cancer. The two XMRV-positive patients were wild type or heterozygous for the R462Q mutation and thus carried at least one fully functional RNase L allele. Conclusions XMRV was rarely detected in non-familial prostate cancer samples from Northern European patients. The homozygous mutation R462Q (QQ) was significantly underrepresented (
Kristin Stieler - One of the best experts on this subject based on the ideXlab platform.
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apobec 3g efficiently reduces infectivity of the human exogenous Gammaretrovirus xmrv
PLOS ONE, 2010Co-Authors: Kristin Stieler, Nicole FischerAbstract:Background The human exogenous Gammaretrovirus XMRV is thought to be implicated in prostate cancer and chronic fatigue syndrome. Besides pressing epidemiologic questions, the elucidation of the tissue and cell tropism of the virus, as well as its sensitivity to retroviral restriction factors is of fundamental importance. The Apobec3 (A3) proteins, a family of cytidine deaminases, are one important group of host proteins that control primary infection and efficient viral spread. Methodology/Principal Findings Here we demonstrate that XMRV is resistant to human Apobec 3B, 3C and 3F, while being highly susceptible to the human A3G protein, a factor which is known to confer antiviral activity against most retroviruses. We show that XMRV as well as MoMLV virions package Apobec proteins independent of their specific restriction activity. hA3G was found to be a potent inhibitor of XMRV as well as of MoMLV infectivity. In contrast to MoMLV, XMRV infection can also be partially reduced by low concentrations of mA3. Interestingly, established prostate cancer cell lines, which are highly susceptible to XMRV infection, do not or only weakly express hA3G. Conclusions Our findings confirm and extend recently published data that show restriction of XMRV infection by hA3G. The results will be of value to explore which cells are infected with XMRV and efficiently support viral spread in vivo. Furthermore, the observation that XMRV infection can be reduced by mA3 is of interest with regard to the current natural reservoir of XMRV infection.
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xenotropic murine leukemia virus related Gammaretrovirus in respiratory tract
Emerging Infectious Diseases, 2010Co-Authors: Nicole Fischer, Kristin Stieler, Claudia Schulz, Christoph Lange, Oliver Höhn, Christian Drosten, Martin AepfelbacherAbstract:Xenotropic murine leukemia virus–related Gammaretrovirus (XMRV) has been recently associated with prostate cancer and chronic fatigue syndrome. To identify nucleic acid sequences, we examined respiratory secretions by using PCR. XMRV-specific sequences were detected in 2%–3% of samples from 168 immunocompetent carriers and ≈10% of samples from 161 immunocompromised patients.
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Host range and cellular tropism of the human exogenous Gammaretrovirus XMRV
Virology, 2010Co-Authors: Kristin Stieler, Martin Aepfelbacher, C. Schulz, M. Lavanya, C. Stocking, N. FischerAbstract:Recently, the first human infection with an exogenous Gammaretrovirus (XMRV) was reported. In its initial description, XMRV was confined to prostate stromal fibroblasts, although subsequent reports demonstrated XMRV protein expression in prostate epithelial cells. Most recently, XMRV has been detected in blood cells of patients with chronic fatigue syndrome. The aim of this study was to elucidate the transmission routes and tissue tropism of XMRV by comparing its host range, receptor usage and LTR functionality with other MLV isolates. We demonstrate using pseudotype experiments that XMRV Env mediates efficient infection of cells from different species. We show that replication competent XMRV infects various human cell types, including hematopoietic cell lines and prostate stromal fibroblasts. XMRV-LTR activity is significantly higher in the prostate cancer cell line LNCaP and in prostate stromal fibroblasts, compared to other cell types tested and could be one factor contributing to efficient viral spread in prostate tissue.
Kazuo Nishigaki - One of the best experts on this subject based on the ideXlab platform.
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Phylogenetic and Structural Diversity in the Feline Leukemia Virus Env Gene
2016Co-Authors: Shinya Watanabe, Yasuyuki Endo, Hajime Tsujimoto, Haruyo Ochi, Yukari Anai, Maki Kawamura, Yuka Odahara, So Nakagawa, Kazuo NishigakiAbstract:Feline leukemia virus (FeLV) belongs to the genus Gammaretrovirus, and causes a variety of neoplastic and non-neoplastic diseases in cats. Alteration of viral env sequences is thought to be associated with disease specificity, but the way in which genetic diversity of FeLV contributes to the generation of such variants in nature is poorly understood. We isolated FeLV env genes from naturally infected cats in Japan and analyzed the evolutionary dynamics of these genes. Phylogenetic reconstructions separated our FeLV samples into three distinct genetic clusters, termed Genotypes I, II, and III. Genotype I is a major genetic cluster and can be further classified into Clades 1–7 in Japan. Genotypes were correlated with geographical distribution; Genotypes I and II were distributed within Japan, whilst FeLV samples from outside Japan belonged to Genotype III. These results may be due to geographical isolation of FeLVs in Japan. The observed structural diversity of the FeLV env gene appears to be caused primarily by mutation, deletion, insertion and recombination, and these variants may be generated de novo in individual cats. FeLV interference assay revealed that FeLV genotypes did not correlate with known FeLV receptor subgroups. We have identified the genotypes which we consider to be reliable for evaluating phylogenetic relationships of FeLV, which embrace the high structural diversity observed in our sample. Overall, these findings extend our understanding of Gammaretrovirus evolutionary patterns in the field, and may provide a useful basis for assessing th
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genetic diversity in the feline leukemia virus gag gene
Virus Research, 2015Co-Authors: Maki Kawamura, Shinya Watanabe, Yasuyuki Endo, Hajime Tsujimoto, Yuka Odahara, So Nakagawa, Kazuo NishigakiAbstract:Feline leukemia virus (FeLV) belongs to the Gammaretrovirus genus and is horizontally transmitted among cats. FeLV is known to undergo recombination with endogenous retroviruses already present in the host during FeLV-subgroup A infection. Such recombinant FeLVs, designated FeLV-subgroup B or FeLV-subgroup D, can be generated by transduced endogenous retroviral env sequences encoding the viral envelope. These recombinant viruses have biologically distinct properties and may mediate different disease outcomes. The generation of such recombinant viruses resulted in structural diversity of the FeLV particle and genetic diversity of the virus itself. FeLV env diversity through mutation and recombination has been studied, while gag diversity and its possible effects are less well understood. In this study, we investigated recombination events in the gag genes of FeLVs isolated from naturally infected cats and reference isolates. Recombination and phylogenetic analyses indicated that the gag genes often contain endogenous FeLV sequences and were occasionally replaced by entire endogenous FeLV gag genes. Phylogenetic reconstructions of FeLV gag sequences allowed for classification into three distinct clusters, similar to those previously established for the env gene. Analysis of the recombination junctions in FeLV gag indicated that these variants have similar recombination patterns within the same genotypes, indicating that the recombinant viruses were horizontally transmitted among cats. It remains to be investigated whether the recombinant sequences affect the molecular mechanism of FeLV transmission. These findings extend our understanding of Gammaretrovirus evolutionary patterns in the field.
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phylogenetic and structural diversity in the feline leukemia virus env gene
PLOS ONE, 2013Co-Authors: Shinya Watanabe, Yasuyuki Endo, Hajime Tsujimoto, Haruyo Ochi, Yukari Anai, Maki Kawamura, Yuka Odahara, So Nakagawa, Kazuo NishigakiAbstract:Feline leukemia virus (FeLV) belongs to the genus Gammaretrovirus, and causes a variety of neoplastic and non-neoplastic diseases in cats. Alteration of viral env sequences is thought to be associated with disease specificity, but the way in which genetic diversity of FeLV contributes to the generation of such variants in nature is poorly understood. We isolated FeLV env genes from naturally infected cats in Japan and analyzed the evolutionary dynamics of these genes. Phylogenetic reconstructions separated our FeLV samples into three distinct genetic clusters, termed Genotypes I, II, and III. Genotype I is a major genetic cluster and can be further classified into Clades 1–7 in Japan. Genotypes were correlated with geographical distribution; Genotypes I and II were distributed within Japan, whilst FeLV samples from outside Japan belonged to Genotype III. These results may be due to geographical isolation of FeLVs in Japan. The observed structural diversity of the FeLV env gene appears to be caused primarily by mutation, deletion, insertion and recombination, and these variants may be generated de novo in individual cats. FeLV interference assay revealed that FeLV genotypes did not correlate with known FeLV receptor subgroups. We have identified the genotypes which we consider to be reliable for evaluating phylogenetic relationships of FeLV, which embrace the high structural diversity observed in our sample. Overall, these findings extend our understanding of Gammaretrovirus evolutionary patterns in the field, and may provide a useful basis for assessing the emergence of novel strains and understanding the molecular mechanisms of FeLV transmission in cats.
