15 results on '"Bannert N"'
Search Results
2. Exploring the functional interaction between POSH and ALIX and the relevance to HIV-1 release
- Author
-
Bannert Norbert, Walther Torsten, Sörgel Stefan, Erez Omri, Taglicht Daniel, Fingrut Orit, Shemesh Vivian, Iavnilovitch Elena, Votteler Jörg, Schubert Ulrich, and Reiss Yuval
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Published
- 2009
- Full Text
- View/download PDF
3. Identification of the protease cleavage sites in a reconstituted Gag polyprotein of an HERV-K(HML-2) element
- Author
-
Kurth Reinhard, Zimmermann Anja, Chudak Claudia, Hohn Oliver, Beimforde Nadine, Schwecke Torsten, George Maja, Naumann Dieter, and Bannert Norbert
- Subjects
HERV-K(HML-2) ,Gag processing ,maturation ,retrovirus ,retroviral protease ,endogenous retrovirus ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background The human genome harbors several largely preserved HERV-K(HML-2) elements. Although this retroviral family comes closest of all known HERVs to producing replication competent virions, mutations acquired during their chromosomal residence have rendered them incapable of expressing infectious particles. This also holds true for the HERV-K113 element that has conserved open reading frames (ORFs) for all its proteins in addition to a functional LTR promoter. Uncertainty concerning the localization and impact of post-insertional mutations has greatly hampered the functional characterization of these ancient retroviruses and their proteins. However, analogous to other betaretroviruses, it is known that HERV-K(HML-2) virions undergo a maturation process during or shortly after release from the host cell. During this process, the subdomains of the Gag polyproteins are released by proteolytic cleavage, although the nature of the mature HERV-K(HML-2) Gag proteins and the exact position of the cleavage sites have until now remained unknown. Results By aligning the amino acid sequences encoded by the gag-pro-pol ORFs of HERV-K113 with the corresponding segments from 10 other well-preserved human specific elements we identified non-synonymous post-insertional mutations that have occurred in this region of the provirus. Reversion of these mutations and a partial codon optimization facilitated the large-scale production of maturation-competent HERV-K113 virus-like particles (VLPs). The Gag subdomains of purified mature VLPs were separated by reversed-phase high-pressure liquid chromatography and initially characterized using specific antibodies. Cleavage sites were identified by mass spectrometry and N-terminal sequencing and confirmed by mutagenesis. Our results indicate that the gag gene product Pr74Gag of HERV-K(HML-2) is processed to yield p15-MA (matrix), SP1 (spacer peptide of 14 amino acids), p15, p27-CA (capsid), p10-NC (nucleocapsid) and two C-terminally encoded glutamine- and proline-rich peptides, QP1 and QP2, spanning 23 and 19 amino acids, respectively. Conclusions Expression of reconstituted sequences of original HERV elements is an important tool for studying fundamental aspects of the biology of these ancient viruses. The analysis of HERV-K(HML-2) Gag processing and the nature of the mature Gag proteins presented here will facilitate further studies of the discrete functions of these proteins and of their potential impact on the human host.
- Published
- 2011
- Full Text
- View/download PDF
4. Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly
- Author
-
Solbak Sara MØ, Studtrucker Nicole, Schmidt Kerstin, Rauch Pia, Hahn Friedrich, Hahn Sabine, Neumann Liane, Votteler Jörg, Fossen Torgils, Henklein Peter, Ott David E, Holland Gudrun, Bannert Norbert, and Schubert Ulrich
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background The HIV-1 p6 Gag protein regulates the final abscission step of nascent virions from the cell membrane by the action of two late assembly (L-) domains. Although p6 is located within one of the most polymorphic regions of the HIV-1 gag gene, the 52 amino acid peptide binds at least to two cellular budding factors (Tsg101 and ALIX), is a substrate for phosphorylation, ubiquitination, and sumoylation, and mediates the incorporation of the HIV-1 accessory protein Vpr into viral particles. As expected, known functional domains mostly overlap with several conserved residues in p6. In this study, we investigated the importance of the highly conserved serine residue at position 40, which until now has not been assigned to any known function of p6. Results Consistently with previous data, we found that mutation of Ser-40 has no effect on ALIX mediated rescue of HIV-1 L-domain mutants. However, the only feasible S40F mutation that preserves the overlapping pol open reading frame (ORF) reduces virus replication in T-cell lines and in human lymphocyte tissue cultivated ex vivo. Most intriguingly, L-domain mediated virus release is not dependent on the integrity of Ser-40. However, the S40F mutation significantly reduces the specific infectivity of released virions. Further, it was observed that mutation of Ser-40 selectively interferes with the cleavage between capsid (CA) and the spacer peptide SP1 in Gag, without affecting cleavage of other Gag products. This deficiency in processing of CA, in consequence, led to an irregular morphology of the virus core and the formation of an electron dense extra core structure. Moreover, the defects induced by the S40F mutation in p6 can be rescued by the A1V mutation in SP1 that generally enhances processing of the CA-SP1 cleavage site. Conclusions Overall, these data support a so far unrecognized function of p6 mediated by Ser-40 that occurs independently of the L-domain function, but selectively affects CA maturation and virus core formation, and consequently the infectivity of released virions.
- Published
- 2011
- Full Text
- View/download PDF
5. Absence of evidence of Xenotropic Murine Leukemia Virus-related virus infection in persons with Chronic Fatigue Syndrome and healthy controls in the United States
- Author
-
Switzer William M, Jia Hongwei, Hohn Oliver, Zheng HaoQiang, Tang Shaohua, Shankar Anupama, Bannert Norbert, Simmons Graham, Hendry R Michael, Falkenberg Virginia R, Reeves William C, and Heneine Walid
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background XMRV, a xenotropic murine leukemia virus (MuLV)-related virus, was recently identified by PCR testing in 67% of persons with chronic fatigue syndrome (CFS) and in 3.7% of healthy persons from the United States. To investigate the association of XMRV with CFS we tested blood specimens from 51 persons with CFS and 56 healthy persons from the US for evidence of XMRV infection by using serologic and molecular assays. Blinded PCR and serologic testing were performed at the US Centers for Disease Control and Prevention (CDC) and at two additional laboratories. Results Archived blood specimens were tested from persons with CFS defined by the 1994 international research case definition and matched healthy controls from Wichita, Kansas and metropolitan, urban, and rural Georgia populations. Serologic testing at CDC utilized a Western blot (WB) assay that showed excellent sensitivity to MuLV and XMRV polyclonal or monoclonal antibodies, and no reactivity on sera from 121 US blood donors or 26 HTLV-and HIV-infected sera. Plasma from 51 CFS cases and plasma from 53 controls were all WB negative. Additional blinded screening of the 51 cases and 53 controls at the Robert Koch Institute using an ELISA employing recombinant Gag and Env XMRV proteins identified weak seroreactivity in one CFS case and a healthy control, which was not confirmed by immunofluorescence. PCR testing at CDC employed a gag and a pol nested PCR assay with a detection threshold of 10 copies in 1 ug of human DNA. DNA specimens from 50 CFS patients and 56 controls and 41 US blood donors were all PCR-negative. Blinded testing by a second nested gag PCR assay at the Blood Systems Research Institute was also negative for DNA specimens from the 50 CFS cases and 56 controls. Conclusions We did not find any evidence of infection with XMRV in our U.S. study population of CFS patients or healthy controls by using multiple molecular and serologic assays. These data do not support an association of XMRV with CFS.
- Published
- 2010
- Full Text
- View/download PDF
6. Lack of evidence for xenotropic murine leukemia virus-related virus(XMRV) in German prostate cancer patients
- Author
-
Miller Kurt, Denner Joachim, Beimforde Nadine, Niederstadt Lars, Barbarotto Pia, Krause Hans, Hohn Oliver, Kurth Reinhard, and Bannert Norbert
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract 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. Results 589 prostate tumor samples were genotyped by real-time PCR with regard to the RNaseL mutation. DNA and RNA samples from these patients were screened for the presence of XMRV-specific gag sequences using a highly sensitive nested PCR and RT-PCR approach. Furthermore, 146 sera samples from prostate tumor patients were tested for XMRV Gag and Env antibodies using a newly developed ELISA assay. In agreement with earlier data, 12.9% (76 samples) were shown to be of the QQ genotype. However, XMRV specific sequences were detected at neither the DNA nor the RNA level. Consistent with this result, none of the sera analyzed from prostate cancer patients contained XMRV-specific antibodies. Conclusion Our results indicate a much lower prevalence (or even complete absence) of XMRV in prostate tumor patients in Germany. One possible reason for this could be a geographically restricted incidence of XMRV infections.
- Published
- 2009
- Full Text
- View/download PDF
7. Vpx enhances innate immune responses independently of SAMHD1 during HIV-1 infection.
- Author
-
Cingöz O, Arnow ND, Puig Torrents M, and Bannert N
- Subjects
- Cell Line, HEK293 Cells, HIV Infections genetics, HIV Infections immunology, HIV-2 physiology, Humans, Leukocytes, Mononuclear virology, Proteolysis, SAM Domain and HD Domain-Containing Protein 1 immunology, SAM Domain and HD Domain-Containing Protein 1 metabolism, THP-1 Cells, Virus Replication, HIV-2 genetics, Host-Pathogen Interactions genetics, Host-Pathogen Interactions immunology, Immunity, Innate genetics, SAM Domain and HD Domain-Containing Protein 1 genetics, Viral Regulatory and Accessory Proteins genetics, Viral Regulatory and Accessory Proteins immunology
- Abstract
Background: The genomes of HIV-2 and some SIV strains contain the accessory gene vpx, which carries out several functions during infection, including the downregulation of SAMHD1. Vpx is also commonly used in experiments to increase HIV-1 infection efficiency in myeloid cells, particularly in studies that investigate the activation of antiviral pathways. However, the potential effects of Vpx on cellular innate immune signaling is not completely understood. We investigated whether and how Vpx affects ISG responses in monocytic cell lines and MDMs during HIV-1 infection., Results: HIV-1 infection at excessively high virus doses can induce ISG activation, although at the expense of high levels of cell death. At equal infection levels, the ISG response is potentiated by the presence of Vpx and requires the initiation of reverse transcription. The interaction of Vpx with the DCAF1 adaptor protein is important for the enhanced response, implicating Vpx-mediated degradation of a host factor. Cells lacking SAMHD1 show similarly augmented responses, suggesting an effect that is independent of SAMHD1 degradation. Overcoming SAMHD1 restriction in MDMs to reach equal infection levels with viruses containing and lacking Vpx reveals a novel function of Vpx in elevating innate immune responses., Conclusions: Vpx likely has as yet undefined roles in infected cells. Our results demonstrate that Vpx enhances ISG responses in myeloid cell lines and primary cells independently of its ability to degrade SAMHD1. These findings have implications for innate immunity studies in myeloid cells that use Vpx delivery with HIV-1 infection.
- Published
- 2021
- Full Text
- View/download PDF
8. Correction to: LEDGINs inhibit late stage HIV-1 replication by modulating integrase multimerization in the virions.
- Author
-
Desimmie BA, Schrijvers R, Demeulemeester J, Borrenberghs D, Weydert C, Thys W, Vets S, Van Remoortel B, Hofkens J, De Rijck J, Hendrix J, Bannert N, Gijsbers R, Christ F, and Debyser Z
- Abstract
An amendment to this paper has been published and can be accessed via the original article.
- Published
- 2020
- Full Text
- View/download PDF
9. Correction to: HIV-1 IN/Pol recruits LEDGF/p75 into viral particles.
- Author
-
Desimmie BA, Weydert C, Schrijvers R, Vets S, Demeulemeester J, Proost P, Paron I, De Rijck J, Mast J, Bannert N, Gijsbers R, Christ F, and Debyser Z
- Abstract
An amendment to this paper has been published and can be accessed via the original article.
- Published
- 2020
- Full Text
- View/download PDF
10. HIV-1 IN/Pol recruits LEDGF/p75 into viral particles.
- Author
-
Desimmie BA, Weydert C, Schrijvers R, Vets S, Demeulemeester J, Proost P, Paron I, De Rijck J, Mast J, Bannert N, Gijsbers R, Christ F, and Debyser Z
- Subjects
- HIV Protease metabolism, Humans, Proteolysis, Adaptor Proteins, Signal Transducing metabolism, HIV-1 physiology, Host-Pathogen Interactions, Transcription Factors metabolism, Virus Integration, Virus Replication, pol Gene Products, Human Immunodeficiency Virus metabolism
- Abstract
Background: The dynamic interaction between HIV and its host governs the replication of the virus and the study of the virus-host interplay is key to understand the viral lifecycle. The host factor lens epithelium-derived growth factor (LEDGF/p75) tethers the HIV preintegration complex to the chromatin through a direct interaction with integrase (IN). Small molecules that bind the LEDGF/p75 binding pocket of the HIV IN dimer (LEDGINs) block HIV replication through a multimodal mechanism impacting early and late stage replication including HIV maturation. Furthermore, LEDGF/p75 has been identified as a Pol interaction partner. This raised the question whether LEDGF/p75 besides acting as a molecular tether in the target cell, also affects late steps of HIV replication., Results: LEDGF/p75 is recruited into HIV-1 particles through direct interaction with the viral IN (or Pol polyprotein) and is a substrate for HIV-1 protease. Incubation in the presence of HIV-1 protease inhibitors resulted in detection of full-length LEDGF/p75 in purified viral particles. We also demonstrate that inhibition of LEDGF/p75-IN interaction by specific mutants or LEDGINs precludes incorporation of LEDGF/p75 in virions, underscoring the specificity of the uptake. LEDGF/p75 depletion did however not result in altered LEDGIN potency., Conclusion: Together, these results provide evidence for an IN/Pol mediated uptake of LEDGF/p75 in viral particles and a specific cleavage by HIV protease. Understanding of the possible role of LEDGF/p75 or its cleavage fragments in the viral particle awaits further experimentation.
- Published
- 2015
- Full Text
- View/download PDF
11. Identification of late assembly domains of the human endogenous retrovirus-K(HML-2).
- Author
-
Chudak C, Beimforde N, George M, Zimmermann A, Lausch V, Hanke K, and Bannert N
- Subjects
- Amino Acid Motifs, Cell Line, Gene Products, gag genetics, Gene Products, gag metabolism, Humans, Microscopy, Electron, Protein Binding, Endogenous Retroviruses physiology, Virus Assembly, Virus Release
- Abstract
Background: Late assembly (L)-domains are protein interaction motifs, whose dysfunction causes characteristic budding defects in enveloped viruses. Three different amino acid motifs, namely PT/SAP, PPXY and YPX(n)L have been shown to play a major role in the release of exogenous retroviruses. Although the L-domains of exogenous retroviruses have been studied comprehensively, little is known about these motifs in endogenous human retroviruses., Results: Using a molecular clone of the human endogenous retrovirus K113 that had been engineered to reverse the presumed non-synonymous postinsertional mutations in the major genes, we identified three functional L-domains of the virus, all located in the Gag p15 protein. A consensus PTAP tetrapeptide serves as the core of a main L-domain for the virus and its inactivation reduces virus release in HEK 293T cells by over 80%. Electron microscopy of cells expressing the PTAP mutant revealed predominantly late budding structures and budding chains at the plasma membrane. The fact that this motif determines subcellular colocalization with Tsg101, an ESCRT-I complex protein known to bind to the core tetrapeptide, supports its role as an L-domain. Moreover, two YPX(n)L motifs providing additional L-domain function were identified in the p15 protein. One is adjacent to the PTAP sequence and the other is in the p15 N-terminus. Mutations in either motif diminishes virus release and induces an L-domain phenotype while inactivation of all three L-domains results in a complete loss of particle release in HEK 293T cells. The flexibility of the virus in the use of L-domains for gaining access to the ESCRT machinery is demonstrated by overexpression of Tsg101 which rescues the release of the YPX(n)L mutants. Similarly, overexpression of Alix not only enhances release of the PTAP mutant by a factor of four but also the release of a triple mutant, indicating that additional cryptic YPX(n)L domains with a low affinity for Alix may be present. No L-domain activity is provided by the proline-rich peptides at the Gag C-terminus., Conclusions: Our data demonstrate that HERV-K(HML-2) release is predominantly mediated through a consensus PTAP motif and two auxiliary YPX(n)L motifs in the p15 protein of the Gag precursor.
- Published
- 2013
- Full Text
- View/download PDF
12. LEDGINs inhibit late stage HIV-1 replication by modulating integrase multimerization in the virions.
- Author
-
Desimmie BA, Schrijvers R, Demeulemeester J, Borrenberghs D, Weydert C, Thys W, Vets S, Van Remoortel B, Hofkens J, De Rijck J, Hendrix J, Bannert N, Gijsbers R, Christ F, and Debyser Z
- Subjects
- Cells, Cultured, Humans, Leukocytes, Mononuclear virology, HIV Integrase metabolism, HIV Integrase Inhibitors metabolism, HIV-1 drug effects, HIV-1 physiology, Protein Multimerization drug effects, Virus Assembly drug effects, Virus Replication drug effects
- Abstract
Background: LEDGINs are novel allosteric HIV integrase (IN) inhibitors that target the lens epithelium-derived growth factor (LEDGF)/p75 binding pocket of IN. They block HIV-1 integration by abrogating the interaction between LEDGF/p75 and IN as well as by allosterically inhibiting the catalytic activity of IN., Results: Here we demonstrate that LEDGINs reduce the replication capacity of HIV particles produced in their presence. We systematically studied the molecular basis of this late effect of LEDGINs and demonstrate that HIV virions produced in their presence display a severe replication defect. Both the late effect and the previously described, early effect on integration contribute to LEDGIN antiviral activity as shown by time-of-addition, qPCR and infectivity assays. The late effect phenotype requires binding of LEDGINs to integrase without influencing proteolytic cleavage or production of viral particles. LEDGINs augment IN multimerization during virion assembly or in the released viral particles and severely hamper the infectivity of progeny virions. About 70% of the particles produced in LEDGIN-treated cells do not form a core or display aberrant empty cores with a mislocalized electron-dense ribonucleoprotein. The LEDGIN-treated virus displays defective reverse transcription and nuclear import steps in the target cells. The LEDGIN effect is possibly exerted at the level of the Pol precursor polyprotein., Conclusion: Our results suggest that LEDGINs modulate IN multimerization in progeny virions and impair the formation of regular cores during the maturation step, resulting in a decreased infectivity of the viral particles in the target cells. LEDGINs thus profile as unique antivirals with combined early (integration) and late (IN assembly) effects on the HIV replication cycle.
- Published
- 2013
- Full Text
- View/download PDF
13. Identification of the protease cleavage sites in a reconstituted Gag polyprotein of an HERV-K(HML-2) element.
- Author
-
George M, Schwecke T, Beimforde N, Hohn O, Chudak C, Zimmermann A, Kurth R, Naumann D, and Bannert N
- Subjects
- Amino Acid Sequence, Chromatography, High Pressure Liquid, Gene Products, gag isolation & purification, Humans, Mass Spectrometry, Molecular Sequence Data, Sequence Alignment, Virosomes genetics, Virosomes isolation & purification, Virosomes metabolism, Endogenous Retroviruses genetics, Gene Products, gag genetics, Gene Products, gag metabolism, Peptide Hydrolases metabolism
- Abstract
Background: The human genome harbors several largely preserved HERV-K(HML-2) elements. Although this retroviral family comes closest of all known HERVs to producing replication competent virions, mutations acquired during their chromosomal residence have rendered them incapable of expressing infectious particles. This also holds true for the HERV-K113 element that has conserved open reading frames (ORFs) for all its proteins in addition to a functional LTR promoter. Uncertainty concerning the localization and impact of post-insertional mutations has greatly hampered the functional characterization of these ancient retroviruses and their proteins. However, analogous to other betaretroviruses, it is known that HERV-K(HML-2) virions undergo a maturation process during or shortly after release from the host cell. During this process, the subdomains of the Gag polyproteins are released by proteolytic cleavage, although the nature of the mature HERV-K(HML-2) Gag proteins and the exact position of the cleavage sites have until now remained unknown., Results: By aligning the amino acid sequences encoded by the gag-pro-pol ORFs of HERV-K113 with the corresponding segments from 10 other well-preserved human specific elements we identified non-synonymous post-insertional mutations that have occurred in this region of the provirus. Reversion of these mutations and a partial codon optimization facilitated the large-scale production of maturation-competent HERV-K113 virus-like particles (VLPs). The Gag subdomains of purified mature VLPs were separated by reversed-phase high-pressure liquid chromatography and initially characterized using specific antibodies. Cleavage sites were identified by mass spectrometry and N-terminal sequencing and confirmed by mutagenesis. Our results indicate that the gag gene product Pr74Gag of HERV-K(HML-2) is processed to yield p15-MA (matrix), SP1 (spacer peptide of 14 amino acids), p15, p27-CA (capsid), p10-NC (nucleocapsid) and two C-terminally encoded glutamine- and proline-rich peptides, QP1 and QP2, spanning 23 and 19 amino acids, respectively., Conclusions: Expression of reconstituted sequences of original HERV elements is an important tool for studying fundamental aspects of the biology of these ancient viruses. The analysis of HERV-K(HML-2) Gag processing and the nature of the mature Gag proteins presented here will facilitate further studies of the discrete functions of these proteins and of their potential impact on the human host.
- Published
- 2011
- Full Text
- View/download PDF
14. Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly.
- Author
-
Votteler J, Neumann L, Hahn S, Hahn F, Rauch P, Schmidt K, Studtrucker N, Solbak SM, Fossen T, Henklein P, Ott DE, Holland G, Bannert N, and Schubert U
- Subjects
- Amino Acid Sequence, Cell Line, Cells, Cultured, Gene Expression Regulation, Viral, HeLa Cells, Humans, Magnetic Resonance Spectroscopy, Microscopy, Electron, Transmission, Molecular Sequence Data, Mutation, T-Lymphocytes, Virion metabolism, Virion ultrastructure, Virus Release, Virus Replication, gag Gene Products, Human Immunodeficiency Virus genetics, Capsid metabolism, Serine genetics, Virus Assembly, gag Gene Products, Human Immunodeficiency Virus chemistry, gag Gene Products, Human Immunodeficiency Virus metabolism
- Abstract
Background: The HIV-1 p6 Gag protein regulates the final abscission step of nascent virions from the cell membrane by the action of two late assembly (L-) domains. Although p6 is located within one of the most polymorphic regions of the HIV-1 gag gene, the 52 amino acid peptide binds at least to two cellular budding factors (Tsg101 and ALIX), is a substrate for phosphorylation, ubiquitination, and sumoylation, and mediates the incorporation of the HIV-1 accessory protein Vpr into viral particles. As expected, known functional domains mostly overlap with several conserved residues in p6. In this study, we investigated the importance of the highly conserved serine residue at position 40, which until now has not been assigned to any known function of p6., Results: Consistently with previous data, we found that mutation of Ser-40 has no effect on ALIX mediated rescue of HIV-1 L-domain mutants. However, the only feasible S40F mutation that preserves the overlapping pol open reading frame (ORF) reduces virus replication in T-cell lines and in human lymphocyte tissue cultivated ex vivo. Most intriguingly, L-domain mediated virus release is not dependent on the integrity of Ser-40. However, the S40F mutation significantly reduces the specific infectivity of released virions. Further, it was observed that mutation of Ser-40 selectively interferes with the cleavage between capsid (CA) and the spacer peptide SP1 in Gag, without affecting cleavage of other Gag products. This deficiency in processing of CA, in consequence, led to an irregular morphology of the virus core and the formation of an electron dense extra core structure. Moreover, the defects induced by the S40F mutation in p6 can be rescued by the A1V mutation in SP1 that generally enhances processing of the CA-SP1 cleavage site., Conclusions: Overall, these data support a so far unrecognized function of p6 mediated by Ser-40 that occurs independently of the L-domain function, but selectively affects CA maturation and virus core formation, and consequently the infectivity of released virions.
- Published
- 2011
- Full Text
- View/download PDF
15. Lack of evidence for xenotropic murine leukemia virus-related virus(XMRV) in German prostate cancer patients.
- Author
-
Hohn O, Krause H, Barbarotto P, Niederstadt L, Beimforde N, Denner J, Miller K, Kurth R, and Bannert N
- Subjects
- Adult, Aged, Aged, 80 and over, Animals, Antibodies, Viral blood, DNA, Viral genetics, DNA, Viral isolation & purification, Enzyme-Linked Immunosorbent Assay, Gene Products, gag genetics, Gene Products, gag immunology, Germany, Humans, Leukemia Virus, Murine genetics, Male, Mice, Middle Aged, Polymerase Chain Reaction methods, Prevalence, Prostatic Neoplasms epidemiology, RNA, Viral genetics, RNA, Viral isolation & purification, Retroviridae Infections virology, Reverse Transcriptase Polymerase Chain Reaction methods, Tumor Virus Infections virology, Viral Envelope Proteins genetics, Viral Envelope Proteins immunology, Leukemia Virus, Murine isolation & purification, Prostatic Neoplasms virology, Retroviridae Infections epidemiology, Tumor Virus Infections epidemiology
- Abstract
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., Results: 589 prostate tumor samples were genotyped by real-time PCR with regard to the RNaseL mutation. DNA and RNA samples from these patients were screened for the presence of XMRV-specific gag sequences using a highly sensitive nested PCR and RT-PCR approach. Furthermore, 146 sera samples from prostate tumor patients were tested for XMRV Gag and Env antibodies using a newly developed ELISA assay. In agreement with earlier data, 12.9% (76 samples) were shown to be of the QQ genotype. However, XMRV specific sequences were detected at neither the DNA nor the RNA level. Consistent with this result, none of the sera analyzed from prostate cancer patients contained XMRV-specific antibodies., Conclusion: Our results indicate a much lower prevalence (or even complete absence) of XMRV in prostate tumor patients in Germany. One possible reason for this could be a geographically restricted incidence of XMRV infections.
- Published
- 2009
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.