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2.
Clin Microbiol Rev ; 29(4): 749-57, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27358491

RESUMO

In 2006, a new virus, xenotropic murine leukemia virus-related virus (XMRV), was discovered in a cohort of U.S. men with prostate cancer. Soon after this initial finding, XMRV was also detected in samples from patients with chronic fatigue syndrome (CFS). The blood community, which is highly sensitive to the threat of emerging infectious diseases since the HIV/AIDS crisis, recommended indefinite deferral of all blood donors with a history of CFS. As XMRV research progressed, conflicting results emerged regarding the importance of this virus in the pathophysiology of prostate cancer and/or CFS. Molecular biologists traced the development of XMRV to a recombination event in a laboratory mouse that likely occurred circa 1993. The virus was propagated via cell lines derived from a tumor present in this mouse and spread through contamination of laboratory samples. Well-controlled experiments showed that detection of XMRV was due to contaminated samples and was not a marker of or a causal factor in prostate cancer or CFS. This paper traces the development of XMRV in the prostate and CFS scientific communities and explores the effect it had on the blood community.


Assuntos
Síndrome de Fadiga Crônica/etiologia , Neoplasias da Próstata/etiologia , Infecções por Retroviridae/complicações , Infecções por Retroviridae/transmissão , Reação Transfusional , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/isolamento & purificação , Animais , Sangue/virologia , Evolução Molecular , Síndrome de Fadiga Crônica/epidemiologia , Humanos , Masculino , Camundongos , Neoplasias da Próstata/epidemiologia , Infecções por Retroviridae/virologia , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/genética
3.
J Clin Invest ; 126(3): 1109-13, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26901817

RESUMO

It has been reported that endogenous retroviruses can contaminate human cell lines that have been passaged as xenotransplants in immunocompromised mice. We previously developed and described 2 human pancreatic ß cell lines (EndoC-ßH1 and EndoC-ßH2) that were generated in this way. Here, we have shown that B10 xenotropic virus 1 (Bxv1), a xenotropic endogenous murine leukemia virus (MuLV), is present in these 2 recently described cell lines. We determined that Bxv1 was also present in SCID mice that were used for in vivo propagation of EndoC-ßH1/2 cells, suggesting that contamination occurred during xenotransplantation. EndoC-ßH1/2 cells released Bxv1 particles that propagated to human 293T and Mus dunni cells. Mobilization assays demonstrated that Bxv1 transcomplements defective MuLV-based retrovectors. In contrast, common rodent ß cell lines, rat INS-1E and RIN-5F cells and mouse MIN6 and ßTC3 cells, displayed either no or extremely weak xenotropic helper activity toward MuLV-based retrovectors, although xenotropic retrovirus sequences and transcripts were detected in both mouse cell lines. Bxv1 propagation from EndoC-ßH1/2 to 293T cells occurred only under optimized conditions and was overall poorly efficient. Thus, although our data imply that MuLV-based retrovectors should be cautiously used in EndoC-ßH1/2 cells, our results indicate that an involuntary propagation of Bxv1 from these cells can be easily avoided with good laboratory practices.


Assuntos
Células Secretoras de Insulina/virologia , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/genética , Animais , Linhagem Celular , Expressão Gênica , Genoma Viral , Xenoenxertos , Humanos , Camundongos , Camundongos SCID , Ratos , Proteínas do Envelope Viral/metabolismo , Integração Viral , Replicação Viral , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/metabolismo
4.
BMC Genomics ; 16: 613, 2015 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-26282858

RESUMO

BACKGROUND: Endogenous murine leukemia retroviruses (MLVs) are high copy number proviral elements difficult to comprehensively characterize using standard low throughput sequencing approaches. However, high throughput approaches generate data that is challenging to process, interpret and present. RESULTS: Next generation sequencing (NGS) data was generated for MLVs from two wild caught Mus musculus domesticus (from mainland France and Corsica) and for inbred laboratory mouse strains C3H, LP/J and SJL. Sequence reads were grouped using a novel sequence clustering approach as applied to retroviral sequences. A Markov cluster algorithm was employed, and the sequence reads were queried for matches to specific xenotropic (Xmv), polytropic (Pmv) and modified polytropic (Mpmv) viral reference sequences. CONCLUSIONS: Various MLV subtypes were more widespread than expected among the mice, which may be due to the higher coverage of NGS, or to the presence of similar sequence across many different proviral loci. The results did not correlate with variation in the major MLV receptor Xpr1, which can restrict exogenous MLVs, suggesting that endogenous MLV distribution may reflect gene flow more than past resistance to infection.


Assuntos
Vírus da Leucemia Murina/classificação , Vírus da Leucemia Murina/genética , RNA Viral/análise , Análise de Sequência de RNA/métodos , Animais , Europa (Continente) , Evolução Molecular , Fluxo Gênico , Vírus da Leucemia Murina/isolamento & purificação , Cadeias de Markov , Camundongos , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/genética
5.
Biotechnol Prog ; 31(2): 431-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25683459

RESUMO

Virus clearance by depth filtration has not been well-understood mechanistically due to lack of quantitative data on filter charge characteristics and absence of systematic studies. It is generally believed that both electrostatic interactions and sized based mechanical entrapment contribute to virus clearance by depth filtration. In order to establish whether the effectiveness of virus clearance correlates with the charge characteristics of a given depth filter, a counter-ion displacement technique was employed to determine the ionic capacity for several depth filters. Two depth filters (Millipore B1HC and X0HC) with significant differences in ionic capacities were selected and evaluated for their ability to eliminate viruses. The high ionic capacity X0HC filter showed complete porcine parvovirus (PPV) clearance (eliminating the spiked viruses to below the limit of detection) under low conductivity conditions (≤2.5 mS/cm), achieving a log10 reduction factor (LRF) of > 4.8. On the other hand, the low ionic capacity B1HC filter achieved only ∼2.1-3.0 LRF of PPV clearance under the same conditions. These results indicate that parvovirus clearance by these two depth filters are mainly achieved via electrostatic interactions between the filters and PPV. When much larger xenotropic murine leukemia virus (XMuLV) was used as the model virus, complete retrovirus clearance was obtained under all conditions evaluated for both depth filters, suggesting the involvement of mechanisms other than just electrostatic interactions in XMuLV clearance.


Assuntos
Filtração/instrumentação , Filtração/métodos , Vírus/isolamento & purificação , Animais , Gatos , Linhagem Celular , Concentração Osmolar , Parvovirus Suíno , Eletricidade Estática , Suínos , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina
6.
Biotechnol Bioeng ; 112(4): 743-50, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25335906

RESUMO

Protein A chromatography is the most common unit operation used in the manufacture of therapeutic monoclonal antibodies (mAbs) due to its high affinity and specificity for the IgG Fc domain. However, protein A chromatography is often not effective for viral clearance. Typical log reduction values (LRV) for the model retrovirus XMuLV range between 1 and 4 logs, while effective steps such as viral filtration can achieve 5-7 logs of clearance. XMuLV LRVs obtained on protein A are reproducible for a given mAb, but can vary widely for different mAbs, even with the same operating conditions. In order to understand the mechanism of XMuLV clearance on protein A, we have investigated its partitioning on Mabselect SuRe protein A resin and explored how the virus interacts with resin, product, and impurities. The results show that XMuLV has some interaction with the resin backbone and ligand, but also appears to bind to and coelute with the mAb. The interaction with product was further examined by evaluating the effect of feed conditions, loading, and different washes on XMuLV partitioning on the column. Understanding the mechanism of XMuLV removal on a protein A, resin provides insight into the variability and low viral clearance of this step and suggests ways in which the removal of virus by this step can be improved.


Assuntos
Anticorpos Monoclonais/isolamento & purificação , Cromatografia de Afinidade/métodos , Proteína Estafilocócica A/metabolismo , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/isolamento & purificação , Meios de Cultura/química
7.
Indian J Cancer ; 52(1): 61-4, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26837976

RESUMO

BACKGROUND: Development of oral cancer, a widely prevalent cancer in India, is multifactorial with increased risk in those habituated to smoking, consuming alcohol and chewing paan and tobacco. This does not preclude other etiological factors in the causation of this cancer. Exploratory studies on several oncogenic viruses have found varied associations with oral cancers. AIM: The aim of this study was to explore the association of xenotropic murine leukemia virus-related virus, (XMRV) a retrovirus recently implicated in oncogenesis in humans, with oral cancers. SETTINGS AND DESIGN: The presence of XMRV proviral deoxyribonucleic acid (DNA) was evaluated by standard nucleic acid amplification from DNA extracted from representative bits of tumor tissues and adjacent normal tissues from surgically resected specimens sent post-operatively for routine histopathological testing. MATERIALS AND METHODS: This prospective study comprised 109 patients with a provisional diagnosis of oral cancer who were operated at the Oral Oncology Department of Kidwai Memorial Institute of Oncology, over a period of 10 months. RESULTS: XMRV was not found in any of the tumor tissues (squamous cell carcinomas - 98; verrucous carcinomas - 4) nor in any of the normal tissues. It is thus important that the absence of this oncogenic virus in all the cases makes the association of XMRV with oral cancers very unlikely. CONCLUSIONS: There is a need to investigate potentially oncogenic viruses in other solid tumors and in larger sample sizes. Any such association could have implications in detecting, preventing and treating these cancers.


Assuntos
Neoplasias Bucais/patologia , Neoplasias Bucais/virologia , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/patogenicidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Humanos , Índia , Masculino , Camundongos , Pessoa de Meia-Idade , Vírus Oncogênicos/patogenicidade , Estudos Prospectivos , Centros de Atenção Terciária
8.
New Microbiol ; 37(4): 543-50, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25387292

RESUMO

Although xenotropic murine leukemia virus-related virus (XMRV) has been regarded as a laboratory contaminant, it remains one of the most controversial viruses. The objective of the study was to determine if XMRV is present in 44 patients with beta-thalassemia major, 48 with sickle cell disease, and 89 volunteer blood donors. After RNA/ DNA extraction from plasma/buffy coat the samples were screened for XMRV sequences by conserved nested GAG primers. None of the RNA samples showed a positive result. Surprisingly, four DNA samples obtained from blood donors were positive for XMRV provirus. The subsequent phylogenetic analysis revealed that these sequences are identical to the positive control (murine leukemia retrovirus) and are probably consistent with laboratory contamination. XMRV infection (provirus and viral RNA) was absent in multiply transfused patients and volunteer blood donors. The positive result obtained from some blood donors probably reflects laboratory contamination. We believe that XMRV does not pose risk to blood transfusion.


Assuntos
Anemia Falciforme/virologia , Infecções por Retroviridae/virologia , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/isolamento & purificação , Talassemia beta/virologia , Adolescente , Adulto , Animais , Doadores de Sangue , Transfusão de Sangue , Brasil , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/classificação , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/genética , Adulto Jovem
9.
J Coll Physicians Surg Pak ; 24(9): 636-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25233966

RESUMO

OBJECTIVE: To determine the association of Xenotropic murine leukemia virus related virus (XMRV) infection with prostate cancer and compare it with benign prostate hyperplasia. STUDY DESIGN: Case control study. PLACE AND DURATION OF STUDY: Department of Histopathology and Molecular Pathology, Dow University of Health Sciences, Karachi, from January 2009 to December 2012. METHODOLOGY: XMRV was screened in 50 prostate cancer and 50 benign prostatic hyperplasia biopsies using conventional end-point PCR. Other studied variables were family history of prostate cancer, patients age and Gleason score. RESULTS: XMRV was detected in 4 (8%) of the 50 prostate cancer biopsy specimens compared to none in biopsies with benign prostatic hyperplasia. However, there was no significant statistical association of XMRV infection with the other variables. CONCLUSION: A low frequency of XMRV infection was found in this case-control study. Men, who harbor XMRV infection, may be at increased risk of prostate cancer but this needs to be investigated further at a larger scale.


Assuntos
Adenocarcinoma/virologia , Próstata/virologia , Hiperplasia Prostática/virologia , Neoplasias da Próstata/virologia , Infecções Tumorais por Vírus/epidemiologia , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/isolamento & purificação , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Biópsia , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Paquistão/epidemiologia , Reação em Cadeia da Polimerase , Próstata/patologia , Hiperplasia Prostática/epidemiologia , Hiperplasia Prostática/patologia , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Provírus/genética , RNA Viral/genética , RNA Viral/isolamento & purificação , Infecções Tumorais por Vírus/virologia , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/genética
10.
Nucleic Acids Res ; 42(17): 11092-106, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25190459

RESUMO

Post-transcriptional regulatory mechanisms of several complex and simple retroviruses and retroelements have been elucidated, with the exception of the gammaretrovirus family. We found that, similar to the other retroviruses, gag gene expression of MuLV and XMRV depends on post-transcriptional regulation mediated via an RNA sequence overlapping the pro-pol open reading frame, termed the Post-Transcriptional Element (PTE). PTE function can be replaced by heterologous RNA export elements, e.g. CTE of simian type D retroviruses. Alternatively, Gag particle production is achieved using an RNA/codon optimized gag gene. PTE function is transferable and can replace HIV Rev-RRE-regulated expression of HIV gag. Analysis of PTE by SHAPE revealed a highly structured RNA comprising seven stem-loop structures, with the 5' and 3' stem-loops forming an essential bipartite signal. MuLV and XMRV PTE share 98% identity and have highly similar RNA structures, with changes mostly located to single-stranded regions. PTE identification strongly suggests that all retroviruses and retroelements share common strategies of post-transcriptional gene regulation to produce Gag. Expression depends on complex RNA structures embedded within retroviral mRNA, in coding regions or the 3' untranslated region. These specific structures serve as recognition signals for either cellular or viral proteins.


Assuntos
Regulação Viral da Expressão Gênica , Vírus da Leucemia Murina de Moloney/genética , RNA Mensageiro/química , RNA Viral/química , Sequências Reguladoras de Ácido Ribonucleico , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/genética , Produtos do Gene gag/genética , Produtos do Gene gag/metabolismo , Células HEK293 , Células HeLa , Humanos , Vírus da Leucemia Murina de Moloney/metabolismo , Conformação de Ácido Nucleico , RNA Mensageiro/metabolismo , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/metabolismo , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética , Produtos do Gene gag do Vírus da Imunodeficiência Humana/metabolismo
11.
Biochimie ; 107 Pt B: 300-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25260582

RESUMO

Xenotropic Murine Leukemia Virus-related Virus (XMRV) is a new gammaretrovirus generated by genetic recombination between two murine endogenous retroviruses, PreXMRV1 and PreXMRV2, during passaging of human prostate cancer xenografts in laboratory mice. XMRV is representative of an early founder virus that jumps species from mouse to human cell lines. Relatively little information is available concerning the XMRV integrase (IN), an enzyme that catalyzes a key stage in the retroviral cycle, and whose sequence is conserved among replication competent retroviruses emerging from recombination between the murine endogenous PreXMRV-1 and PreXMRV-2 genomes. Previous studies have shown that IN inhibitors efficiently block XMRV multiplication in cells. We thus aimed at characterizing the biochemical properties and sensitivity of the XMRV IN to the raltegravir, dolutegravir, 118-D-24 and elvitegravir inhibitors in vitro. We report for the first time the purification and enzymatic characterization of recombinant XMRV IN. This IN, produced in Escherichia coli and purified under native conditions, is optimally active over a pH range of 7-8.5, in the presence of Mg(2+) (15 mM and 30 mM for 3'-processing and strand transfer, respectively) and is poorly sensitive to the addition of dithiothreitol. Raltegravir was shown to be a very potent inhibitor (IC50 âˆ¼ 30 nM) whereas dolutegravir and elvitegravir were less effective (IC50 âˆ¼ 230 nM and 650 nM, respectively). The 118-D-24 drug had no impact on XMRV IN activity. Interestingly, the substrate specificity of XMRV IN seems to be less marked compared to HIV-1 IN since XMRV IN is able to process various donor substrates that share little homology. Finally, our analysis revealed some original properties of the XMRV IN such as its relatively low sequence specificity.


Assuntos
Inibidores de Integrase/farmacologia , Integrases/química , Integrases/metabolismo , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/enzimologia , Sequência de Aminoácidos , Ditiotreitol/farmacologia , Integrase de HIV/química , Compostos Heterocíclicos com 3 Anéis/farmacologia , Concentração de Íons de Hidrogênio , Integrases/genética , Integrases/isolamento & purificação , Dados de Sequência Molecular , Oxazinas , Piperazinas , Piridonas , Pirrolidinonas/farmacologia , Quinolonas/farmacologia , Raltegravir Potássico , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Homologia de Sequência de Aminoácidos , Especificidade por Substrato , Proteínas Virais/química , Proteínas Virais/genética , Proteínas Virais/metabolismo
12.
BMC Res Notes ; 7: 461, 2014 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-25092471

RESUMO

BACKGROUND: In 2009, a retrospective study reported the detection of xenotropic murine leukemia virus-related virus (XMRV) in clinical isolates derived from individuals with chronic fatigue syndrome or myalgic encephalomyelitis (CFS). While many efforts to confirm this observation failed, one report detected polytropic murine leukemia virus (pMLV), instead of XMRV. In both studies, Polymerase Chain Reaction (PCR)-based methods were employed which could provide the basis for the development of a practical diagnostic tool. To confirm these studies, we hypothesized that the ability to detect these viruses will not only depend upon the technical details of the methods employed but also on the criteria used to diagnose CFS and the availability of well characterized clinical isolates. METHODS: A repository of clinical isolates from geographically distinct sites was generated by the collection of fresh blood samples from well characterized CFS and healthy subjects. Molecular techniques were used to generate assay positive controls and to determine the lower limit of detection (LLOD) for murine retroviral and Intracisternal A particle (Cell 12(4):963-72, 1977) detection methods. RESULTS: We report the establishment of a repository of well-defined, clinical isolates from five, geographically distinct regions of the US, the comparative determination of the LLODs and validation efforts for the previously reported detection methods and the results of an effort to confirm the association of these retroviral signatures in isolates from individuals with CFS in a blinded, multi-site, prospective study. We detected various, murine retroviral DNA signatures but were unable to resolve a difference in the incidence of their detection between isolates from CFS (5/72; 6.7%) and healthy (2/37; 5.4%) subjects (Fisher's Exact Test, p-value = 1). The observed sequences appeared to reflect the detection of endogenous murine retroviral DNA, which was not identical to either XMRV or pMLV. CONCLUSIONS: We were unable to confirm a previously reported association between the detection of XMRV or pMLV sequences and CFS in a prospective, multi-site study. Murine retroviral sequences were detected at a low frequency that did not differ between CFS and control subjects. The nature of these sequences appeared to reflect the detection of pre-existing, endogenous, murine retroviral DNA in the PCR reagents employed.


Assuntos
Bancos de Espécimes Biológicos , Síndrome de Fadiga Crônica/virologia , Vírus da Leucemia Murina/isolamento & purificação , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/isolamento & purificação , Adulto , Animais , Sequência de Bases , Estudos de Casos e Controles , DNA Viral/genética , DNA Viral/isolamento & purificação , Demografia , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Filogenia , Reação em Cadeia da Polimerase , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Proteínas Virais/metabolismo
13.
PLoS One ; 9(7): e101367, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25010677

RESUMO

The global AIDS pandemic continues to expand and in some regions of the world, such as southern Africa, the prevalence of HIV-1 infection exceeds 20%. The devastating spread of the virus in young women in these countries appears disproportional to overall risk of infection. Regions with high prevalence of HIV-1 are often also highly endemic for other pathogenic viruses including HSV, CMV and HTLV. We propose that acquisition by HIV-1 of the envelope glycoproteins of other viruses, in a process we call "natural pseudotyping," expands the cellular tropism of HIV-1, enabling it to infect female genital epithelial cells directly and thereby dramatically increasing risk of infection during sexual intercourse. In this proof-of-concept study, we demonstrate that when HIV-1 co-infects T cells along with the gammaretrovirus xenotropic murine leukemia virus-related virus (XMRV), progeny HIV-1 particles are produced capable of infecting primary vaginal, ectocervical and endocervical epithelial cells. These cell types are normally resistant to HIV-1 infection. Infection of primary genital cells was neutralized by antisera against the XMRV glycoprotein, confirming that infection was mediated by the XMRV glycoprotein acquired through pseudotyping of HIV. Inhibition by AZT showed that active replication of HIV-1 occurred in these cells and ruled out non-specific endocytic uptake of the virus. These results demonstrate that natural pseudotyping can expand the tropism of HIV-1 to include genital epithelial cells and have potential implications for sexual transmission of the virus.


Assuntos
Colo do Útero/citologia , Coito , Células Epiteliais/virologia , Infecções por HIV/transmissão , HIV-1/fisiologia , Vagina/citologia , Anticorpos Neutralizantes/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Linhagem Celular , Feminino , HIV-1/imunologia , Humanos , Tropismo Viral , Replicação Viral , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/fisiologia
14.
Rev Soc Bras Med Trop ; 47(3): 302-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25075480

RESUMO

INTRODUCTION: This study confirmed the absence of natural infection with Xenotropic murine leukemia virus-related virus (XMRV) or XMRV-related disease in human populations of the Brazilian Amazon basin. We demonstrated that 803 individuals of both sexes, who were residents of Belem in the Brazilian State of Pará, were not infected with XMRV. METHODS: Individuals were divided into 4 subgroups: healthy individuals, individuals infected with human immunodeficiency virus, type 1 (HIV-1), individuals infected with human T-lymphotrophic virus, types 1 or 2 (HTLV-1/2), and individuals with prostate cancer. XMRV infection was investigated by nested PCR to detect the viral gag gene and by quantitative PCR to detect pol. RESULTS: There was no amplification of either gag or pol segments from XRMV in any of the samples examined. CONCLUSIONS: This study supports the conclusions of the studies that eventually led to the retraction of the original study reporting the association between XMRV and human diseases.


Assuntos
Infecções por HIV/virologia , Infecções por HTLV-I/virologia , Infecções por HTLV-II/virologia , Neoplasias da Próstata/virologia , Infecções por Retroviridae/complicações , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/genética , Adulto , Brasil , DNA Viral/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase
15.
Rev. Soc. Bras. Med. Trop ; 47(3): 302-306, May-Jun/2014. tab, graf
Artigo em Inglês | LILACS | ID: lil-716392

RESUMO

Introduction This study confirmed the absence of natural infection with Xenotropic murine leukemia virus-related virus (XMRV) or XMRV-related disease in human populations of the Brazilian Amazon basin. We demonstrated that 803 individuals of both sexes, who were residents of Belem in the Brazilian State of Pará, were not infected with XMRV. Methods Individuals were divided into 4 subgroups: healthy individuals, individuals infected with human immunodeficiency virus, type 1 (HIV-1), individuals infected with human T-lymphotrophic virus, types 1 or 2 (HTLV-1/2), and individuals with prostate cancer. XMRV infection was investigated by nested PCR to detect the viral gag gene and by quantitative PCR to detect pol. Results There was no amplification of either gag or pol segments from XRMV in any of the samples examined. Conclusions This study supports the conclusions of the studies that eventually led to the retraction of the original study reporting the association between XMRV and human diseases. .


Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por HIV/virologia , Infecções por HTLV-I/virologia , Infecções por HTLV-II/virologia , Neoplasias da Próstata/virologia , Infecções por Retroviridae/complicações , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/genética , Brasil , DNA Viral/genética , Reação em Cadeia da Polimerase
16.
PLoS Med ; 11(4): e1001623, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24714396

RESUMO

Kumanan Wilson and colleagues explain how the rapid response to XMRV as a novel pathogen has highlighted some challenges pertaining to policy-making and editorial responsibilities. The impact on policy and the propagation of the initial scientific information may not cease if the evidence is disproven and retracted from the peer-reviewed literature, which creates a challenge for regulators and scientific journals. Please see later in the article for the Editors' Summary.


Assuntos
Políticas Editoriais , Política de Saúde/legislação & jurisprudência , Formulação de Políticas , Saúde Pública/legislação & jurisprudência , Infecções por Retroviridae/transmissão , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/fisiologia , Doadores de Sangue , Humanos , Infecções por Retroviridae/prevenção & controle , Infecções por Retroviridae/virologia
17.
Biochem Biophys Res Commun ; 447(1): 216-22, 2014 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-24721431

RESUMO

Xenotropic murine leukemia virus-related virus (XMRV) is a novel gammaretrovirus that was originally isolated from human prostate cancer. It is now believed that XMRV is not the etiologic agent of prostate cancer. An analysis of murine leukemia virus (MLV) infection in various human cell lines revealed that prostate cancer cell lines are preferentially infected by XMRV, and this suggested that XMRV infection may confer some sort of growth advantage to prostate cancer cell lines. To examine this hypothesis, androgen-dependent LNCaP cells were infected with XMRV and tested for changes in certain cell growth properties. We found that XMRV-infected LNCaP cells can proliferate in the absence of the androgen dihydrotestosterone. Moreover, androgen receptor expression is significantly reduced in XMRV-infected LNCaP cells. Such alterations were not observed in uninfected and amphotropic MLV-infected LNCaP cells. This finding explains why prostate cancer cell lines are preferentially infected with XMRV.


Assuntos
Androgênios/farmacologia , Proliferação de Células/efeitos dos fármacos , Neoplasias da Próstata/virologia , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/fisiologia , Antagonistas de Receptores de Andrógenos/farmacologia , Anilidas/farmacologia , Animais , Linhagem Celular Tumoral , Di-Hidrotestosterona/farmacologia , Humanos , Masculino , Camundongos , Nitrilas/farmacologia , Ratos , Receptores Androgênicos/biossíntese , Receptores Androgênicos/efeitos dos fármacos , Compostos de Tosil/farmacologia
18.
PLoS One ; 9(3): e91433, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24618588

RESUMO

Cell cultures used routinely in proteomic experiments may contain proteins from other species because of infection, transfection or just contamination. Since infection or contamination may affect the results of a biological experiment, it is important to test the samples for the presence of "alien" proteins. Usually cells are tested only for the most common infections, and most of the existing tests are targeting specific contaminations. Here we describe a three-step procedure for reliable untargeted detection of viral proteins using proteomics data, and recommend this or similar procedure to be applied to every proteomics dataset submitted for publication.


Assuntos
Proteoma , Proteômica , Proteínas Virais/metabolismo , Linhagem Celular , Conjuntos de Dados como Assunto , Regulação Viral da Expressão Gênica , Células HEK293 , Humanos , Proteômica/métodos , Proteínas Virais/genética , Fluxo de Trabalho , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/genética , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/metabolismo
19.
Cell Host Microbe ; 15(3): 255-9, 2014 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-24629332

RESUMO

Xenotropic murine leukemia virus-related virus (XMRV) infection was incorrectly associated with prostate cancer and chronic fatigue syndrome (CFS) in recent years. In this forum, we discuss the story of XMRV and how we can apply lessons learned here to inform the debate surrounding cancers associated with human endogenous retroviruses (HERVs).


Assuntos
Neoplasias/etiologia , Neoplasias/virologia , Infecções por Retroviridae/complicações , Infecções por Retroviridae/virologia , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/isolamento & purificação , Humanos
20.
Appl Environ Microbiol ; 80(8): 2617-22, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24532072

RESUMO

Xenotropic murine leukemia virus-related virus (XMRV) represents a novel γ-retrovirus that is capable of infecting human cells and has been classified as a biosafety level 2 (BSL-2) organism. Hence, XMRV represents a potential risk for personnel in laboratories worldwide. Here, we measured the stability of XMRV and its susceptibility to alcohol-based disinfectants. To this end, we exposed an infectious XMRV reporter virus encoding a secretable luciferase to different temperatures, pH values, and disinfectants and infected XMRV-permissive Raji B cells to measure residual viral infectivity. We found that 1 min treatment of XMRV particles at 60°C is sufficient to reduce infectivity by 99.9%. XMRV infectivity was maximal at a neutral pH but was reduced by 86% at pH 4 and 99.9% at pH 10. The common hand and surface disinfectants ethanol and isopropanol as well as the cell fixation reagent paraformaldehyde abrogated XMRV infectivity entirely, as indicated by a reduction of infectivity exceeding 99.99%. Our findings provide evidence of specific means to inactivate XMRV. Their application will help to prevent unintended XMRV contamination of cell cultures in laboratories and minimize the risk for laboratory personnel and health care workers to become infected with this biosafety level 2 organism.


Assuntos
Álcoois/farmacologia , Desinfetantes/farmacologia , Microbiologia Ambiental , Viabilidade Microbiana/efeitos dos fármacos , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/efeitos dos fármacos , Vírus Relacionado ao Vírus Xenotrópico da Leucemia Murina/fisiologia , Linfócitos B/virologia , Linhagem Celular , Humanos , Concentração de Íons de Hidrogênio , Temperatura
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