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multiple integrated copies and high-level production of the human retrovirus xmrv (xenotropic murine leukemia virus-related virus) from 22rv1 prostate carcinoma cells.the human retrovirus xmrv (xenotropic murine leukemia virus-related virus) is associated with prostate cancer, most frequently in humans with a defect in the antiviral defense protein rnase l, suggesting a role for xmrv in prostate carcinogenesis. however, xmrv has not been found in prostate carcinoma cells. here we show that 22rv1 prostate carcinoma cells produce high-titer virus that is nearly identical in properties and sequence to xmrv isolated by others and consist primarily of a single clo ...200919403664
prevalence of human gammaretrovirus xmrv in sporadic prostate cancer.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.200818823818
a natural human retrovirus efficiently complements vectors based on murine leukemia virus.murine leukemia virus (mlv) is a rodent gammaretrovirus that serves as the backbone for common gene delivery tools designed for experimental and therapeutic applications. recently, an infectious gammaretrovirus designated xmrv has been identified in prostate cancer patients. the similarity between the mlv and xmrv genomes suggests a possibility that the two viruses may interact when present in the same cell.200818769545
integration site preference of xenotropic murine leukemia virus-related virus, a new human retrovirus associated with prostate cancer.xenotropic murine leukemia virus-related virus (xmrv) is a new human gammaretrovirus identified in prostate cancer tissue from patients homozygous for a reduced-activity variant of the antiviral enzyme rnase l. neither a casual relationship between xmrv infection and prostate cancer nor a mechanism of tumorigenesis has been established. to determine the integration site preferences of xmrv and the potential risk of proviral insertional mutagenesis, we carried out a genome-wide analysis of viral ...200818684813
quantification of reverse transcriptase in als and elimination of a novel retroviral candidate.retroviral involvement in amyotrophic lateral sclerosis (als) has been suspected for several years since the recognition that both murine and human retroviruses can cause als-like syndromes. nonquantitative studies have demonstrated the retroviral enzyme reverse transcriptase (rt) in als patients' sera, but the amount and source of rt activity are unknown. we therefore developed a quantitative assay to study rt levels in als and examined the possibility that the recently discovered human gammare ...200818209202
an infectious retrovirus susceptible to an ifn antiviral pathway from human prostate tumors.we recently reported identification of a previously undescribed gammaretrovirus genome, xenotropic murine leukemia virus-related virus (xmrv), in prostate cancer tissue from patients homozygous for a reduced activity variant of the antiviral enzyme rnase l. here we constructed a full-length xmrv genome from prostate tissue rna and showed that the molecular viral clone is replication-competent. xmrv replication in the prostate cancer cell line du145 was sensitive to inhibition by ifn-beta. howeve ...200717234809
identification of a novel gammaretrovirus in prostate tumors of patients homozygous for r462q rnasel variant.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 c ...200616609730
susceptibility of xenotropic murine leukemia virus-related virus (xmrv) to retroviral restriction factors.xenotropic murine leukemia virus-related virus (xmrv) is a recently discovered gammaretrovirus that has been linked to prostate cancer and chronic fatigue syndrome. this virus is therefore an important potential human pathogen and, as such, it is essential to understand its host cell tropism. intriguingly, infectious virus has been recovered from patient-derived peripheral blood mononuclear cells. these cells express several antiviral restriction factors that are capable of inhibiting the replic ...201020194752
chronic fatigue syndrome and human retrovirus xmrv. 201020185494
fidelity of target site duplication and sequence preference during integration of xenotropic murine leukemia virus-related virus.xenotropic murine leukemia virus (mlv)-related virus (xmrv) is a new human retrovirus associated with prostate cancer and chronic fatigue syndrome. the causal relationship of xmrv infection to human disease and the mechanism of pathogenicity have not been established. during retrovirus replication, integration of the cdna copy of the viral rna genome into the host cell chromosome is an essential step and involves coordinated joining of the two ends of the linear viral dna into staggered sites on ...201020421928
prevalence of xenotropic murine leukaemia virus-related virus in patients with chronic fatigue syndrome in the netherlands: retrospective analysis of samples from an established cohort.the presence of the retrovirus xenotropic murine leukaemia virus-related virus (xmrv) has been reported in peripheral blood mononuclear cells of patients with chronic fatigue syndrome. considering the potentially great medical and social relevance of such a discovery, we investigated whether this finding could be confirmed in an independent european cohort of patients with chronic fatigue syndrome.201020185493
absence of xenotropic murine leukaemia virus-related virus in uk patients with chronic fatigue syndrome.detection of a retrovirus, xenotropic murine leukaemia virus-related virus (xmrv), has recently been reported in 67% of patients with chronic fatigue syndrome. we have studied a total of 170 samples from chronic fatigue syndrome patients from two uk cohorts and 395 controls for evidence of xmrv infection by looking either for the presence of viral nucleic acids using quantitative pcr (limit of detection <16 viral copies) or for the presence of serological responses using a virus neutralisation a ...201020156349
retroviral infection in vivo requires an immune escape virulence factor encrypted in the envelope protein of oncoretroviruses.we previously delineated a highly conserved immunosuppressive (is) domain within murine and primate retroviral envelope proteins (envs). the envelope-mediated immunosuppression was manifested by the ability of the proteins, when expressed by allogeneic tumor cells normally rejected by engrafted mice, to allow these cells to escape, at least transiently, immune rejection. using this approach, we identified key residues whose mutation specifically abolishes is activity without affecting the "mecha ...201020142478
the path well traveled: using mammalian retroviruses to guide research on xmrv. 201020124560
comment on "detection of an infectious retrovirus, xmrv, in blood cells of patients with chronic fatigue syndrome".lombardi et al. (reports, 23 october 2009, p. 585) reported an association between the human gammaretrovirus xmrv and chronic fatigue syndrome. however, their results may be misleading because of various potential sources of bias and confounding. if real, the association may lack generalizability because of the specific characteristics of the cases studied and could be due to reverse causality.201020466906
host range and cellular tropism of the human exogenous gammaretrovirus xmrv.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 l ...201020110097
failure to detect the novel retrovirus xmrv in chronic fatigue syndrome.in october 2009 it was reported that 68 of 101 patients with chronic fatigue syndrome (cfs) in the us were infected with a novel gamma retrovirus, xenotropic murine leukaemia virus-related virus (xmrv), a virus previously linked to prostate cancer. this finding, if confirmed, would have a profound effect on the understanding and treatment of an incapacitating disease affecting millions worldwide. we have investigated cfs sufferers in the uk to determine if they are carriers of xmrv.201020066031
xenotropic murine leukemia virus-related gammaretrovirus in respiratory tract.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 approximately 10% of samples from 161 immunocompromised patients.201020507757
xenotropic murine leukemia virus-related virus establishes an efficient spreading infection and exhibits enhanced transcriptional activity in prostate carcinoma cells.xenotropic murine leukemia virus-related virus (xmrv) is a novel human gammaretrovirus discovered in association with human prostate tumors. xmrv was first identified in prostate stromal cells surrounding the tumors of patients carrying a mutation in the hpc1 gene locus. to determine the tropism of xmrv in cell culture, we tested the ability of xmrv to spread and replicate in various prostate and nonprostate cell lines. we found that although the expression of xmrv viral proteins and the spread ...201020015990
identification of viral infections in the prostate and evaluation of their association with cancer.several viruses with known oncogenic potential infect prostate tissue, among these are the polyomaviruses bkv, jcv, and sv40; human papillomaviruses (hpvs), and human cytomegalovirus (hcmv) infections. recently, the xenotropic murine leukemia virus-related gammaretrovirus (xmrv) was identified in prostate tissue with a high prevalence observed in prostate cancer (pc) patients homozygous for the glutamine variant of the rnasel protein (462q/q). association studies with the r462q allele and non-xm ...201020576103
the prostate cancer-associated human retrovirus xmrv lacks direct transforming activity but can induce low rates of transformation in cultured cells.the human retrovirus xmrv (xenotropic murine leukemia virus-related virus) is associated with prostate cancer, but a causal relationship has not been established. here, we have used cultured fibroblast and epithelial cell lines to test the hypothesis that xmrv might have direct transforming activity but found only rare transformation events, suggestive of indirect transformation, even when the target cells expressed the human xpr1 cell entry receptor for xmrv. characterization of cells from thre ...201020007266
xenotropic murine leukemia virus-related virus is susceptible to azt.the xenotropic murine leukemia virus-related virus (xmrv) is a human retrovirus, recently isolated from tissues of prostate cancer patients with impaired rnase l activity. in this study, we evaluated 10 licensed anti-hiv-1 compounds for their activity against xmrv, including protease inhibitors (pi), nucleoside reverse transcriptase (rt) inhibitors (nrti), non-nucleoside rt inhibitors (nnrti) and an integrase inhibitor. no pi affected xmrv production; even high concentrations of ritonavir failed ...201019959199
androgen stimulates transcription and replication of xenotropic murine leukemia virus-related virus.xenotropic murine leukemia virus-related virus (xmrv) is a gammaretrovirus originally identified in a subset of prostate cancer patients. because androgens stimulate prostate tumors and some retroviruses, we investigated the effects of dihydrotestosterone (dht) on xmrv transcription and replication. transcription from the xmrv u3 region was stimulated up to 2-fold by dht, but only in cells containing a functional androgen receptor. mutations in the glucocorticoid response element (gre) of xmrv i ...201019906923
can detection of xenotropic murine leukemia virus-related virus be linked to chronic fatigue syndrome? 201020629499
lack of evidence for xenotropic murine leukemia virus-related virus(xmrv) in german prostate cancer patients.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 ...200919835577
detection of an infectious retrovirus, xmrv, in blood cells of patients with chronic fatigue syndrome.chronic fatigue syndrome (cfs) is a debilitating disease of unknown etiology that is estimated to affect 17 million people worldwide. studying peripheral blood mononuclear cells (pbmcs) from cfs patients, we identified dna from a human gammaretrovirus, xenotropic murine leukemia virus-related virus (xmrv), in 68 of 101 patients (67%) as compared to 8 of 218 (3.7%) healthy controls. cell culture experiments revealed that patient-derived xmrv is infectious and that both cell-associated and cell-fr ...200919815723
six host range variants of the xenotropic/polytropic gammaretroviruses define determinants for entry in the xpr1 cell surface receptor.the evolutionary interactions between retroviruses and their receptors result in adaptive selection of restriction variants that can allow natural populations to evade retrovirus infection. the mouse xenotropic/polytropic (x/pmv) gammaretroviruses rely on the xpr1 cell surface receptor for entry into host cells, and polymorphic variants of this receptor have been identified in different rodent species.200919811656
xmrv is present in malignant prostatic epithelium and is associated with prostate cancer, especially high-grade tumors.xenotropic murine leukemia virus-related virus (xmrv) was recently discovered in human prostate cancers and is the first gammaretrovirus known to infect humans. while gammaretroviruses have well-characterized oncogenic effects in animals, they have not been shown to cause human cancers. we provide experimental evidence that xmrv is indeed a gammaretrovirus with protein composition and particle ultrastructure highly similar to moloney murine leukemia virus (momlv), another gammaretrovirus. we ana ...200919805305
unintended spread of a biosafety level 2 recombinant retrovirus.contamination of vertebrate cell lines with animal retroviruses has been documented repeatedly before. although such viral contaminants can be easily identified with high sensitivity by pcr, it is impossible to screen for all potential contaminants. therefore, we explored two novel methods to identify viral contaminations in cell lines without prior knowledge of the kind of contaminant.200919772602
fibrils of prostatic acid phosphatase fragments boost infections with xmrv (xenotropic murine leukemia virus-related virus), a human retrovirus associated with prostate cancer.the xenotropic murine leukemia virus-related virus (xmrv) has recently been detected in prostate cancer tissues and may play a role in tumorigenesis. it is currently unclear how this virus is transmitted and which factors promote its spread in the prostate. we show that amyloidogenic fragments known as semen-derived enhancer of virus infection (sevi) originating from prostatic acid phosphatase greatly increase xmrv infections of primary prostatic epithelial and stromal cells. hybrid simian/human ...200919403677
[rnase l, a crucial mediator of innate immunity and other cell functions].the 2-5a/rnase l pathway is one of the first cellular defences against viruses. rnase l is an unusual endoribonuclease which activity is strictly regulated by its binding to a small oligonucleotide, 2-5a. 2-5a itself is very unusual, consisting of a series of 5'- triphosphorylated oligoadenylates with 2'-5' bonds. but rnase l activity is not limited to viral rna cleavage. rnase l plays a central role in innate immunity, apoptosis, cell growth and differentiation by regulating cellular rna stabil ...200818950583
detection of a gammaretrovirus, xmrv, in the human population: open questions and implications for xenotransplantation.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 a ...201020219088
[new human retrovirus.]. 201020303544
susceptibility of the human retrovirus xmrv to antiretroviral inhibitors.xmrv (xenotropic murine leukemia virus-related virus) is the first known example of an exogenous gammaretrovirus that can infect humans. a limited number of reports suggest that xmrv is intrinsically resistant to many of the antiretroviral drugs used to treat hiv-1 infection, but is sensitive to a small subset of these inhibitors. in the present study, we used a novel marker transfer assay to directly compare the antiviral drug sensitivities of xmrv and hiv-1 under identical conditions in the sa ...201020807431
evaluation of cellular determinants required for in vitro xenotropic murine leukemia virus-related virus entry into human prostate cancer and noncancerous cells.the newly identified retrovirus-the xenotropic murine leukemia virus-related virus (xmrv)-has recently been shown to be strongly associated with familial prostate cancer in humans (a. urisman et al., plos pathog. 2:e25, 2006). while that study showed evidence of xmrv infection exclusively in the prostatic stromal fibroblasts, a recent study found xmrv protein antigens mainly in malignant prostate epithelial cells (r. schlaberg et al., proc. natl. acad. sci. u. s. a. 106:16351-16356, 2009). to he ...201020410264
xenotropic murine leukemia virus-related virus in chronic fatigue syndrome and prostate cancer.xenotropic murine leukemia virus-related virus (xmrv) is a gamma retrovirus that has been associated with chronic fatigue syndrome (cfs) and prostate cancer. the search for viral causes of these syndromes was reignited by the finding that rnase l activity was low in hereditary prostate cancer and some cfs patients. the six strains of xmrv that have been sequenced have greater than 99% identity, indicating a new human infection rather than laboratory contamination. dna, rna, and proteins from xmr ...201020425007
polymorphisms in inflammatory genes, plasma antioxidants, and prostate cancer risk.presence of xenotropic murine leukemia virus-related virus and chronic inflammation in prostate tumor suggests that inflammation plays a role in prostate cancer etiology. this study investigated whether variants in inflammatory genes act alone or interact with plasma antioxidants to influence prostate cancer risk in a population-based case-control study in central arkansas.201020431935
comment on "detection of an infectious retrovirus, xmrv, in blood cells of patients with chronic fatigue syndrome".lombardi et al. (reports, 23 october 2009, p. 585) reported detection of the human gammaretrovirus xmrv in the blood cells of patients with chronic fatigue syndrome (cfs). however, the patient description provided was incomplete. the inclusion of patients from a "cfs outbreak" previously linked with a viral infection, without confirmation in sporadic cfs cases, casts doubt on the role of xmrv in the pathogenesis of cfs.201020466904
comment on "detection of an infectious retrovirus, xmrv, in blood cells of patients with chronic fatigue syndrome".lombardi et al. (reports, 23 october 2009, p. 585) reported a significant association between the human retrovirus xmrv and chronic fatigue syndrome (cfs). however, the cases with cfs and the control subjects in their study are poorly described and unlikely to be representative. independent replication is a critical first step before accepting the validity of this finding.201020466905
chronic fatigue syndrome: xenotropic murine leukemia virus-related virus, murine leukemia virus, both, or neither? 201020884850
acutely transforming retrovirus expressing nras generated from ht-1080 fibrosarcoma cells infected with the human retrovirus xmrv.virus from ht-1080 fibrosarcoma cells infected with the human retrovirus xmrv (xenotropic murine leukemia virus-related virus) can induce rare foci of transformation in rat 208f fibroblasts. characterization of three such foci revealed that one produced an acutely transforming virus at a high titer. the virus consists of a mutant nras cdna from the ht-1080 cells inserted into a retroviral vector (added to the ht-1080 cells as a marker for infection) in place of internal vector sequences. these r ...201020504941
characterization of retroviral and lentiviral vectors pseudotyped with xenotropic murine leukemia virus-related virus envelope glycoprotein.retroviral and lentiviral vectors are effective gene delivery vehicles that are being evaluated in clinical trials. variations in the viral envelope (env) glycoproteins, which are used to pseudotype retroviral or lentiviral vectors, can alter vector performance, including stability, titers, host range, and tissue tropism. xenotropic murine leukemia virus (mlv)-related virus (xmrv) is a novel human retrovirus identified in patients with prostate cancer. xmrv targets xpr1 cell surface receptor, wh ...201020507233
the human retrovirus xmrv in prostate cancer and chronic fatigue syndrome.xenotropic murine leukemia virus-related virus (xmrv) is an authentic, newly recognized human retrovirus first identified in prostate cancer tissues from men with a deficiency in the innate immunity gene rnasel. at present, studies have detected xmrv at widely different rates in prostate cancer cases (0-27%) and in patients with chronic fatigue syndrome (cfs; 0-67%). indirect or direct modes of carcinogenesis by xmrv have been suggested depending on whether the virus was found in stroma or malig ...201020517289
absence of evidence of xenotropic murine leukemia virus-related virus infection in persons with chronic fatigue syndrome and healthy controls in the united states.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 cont ...201020594299
chronic fatigue syndrome. conflicting papers on hold as xmrv frenzy reaches new heights. 201020595585
absence of xenotropic murine leukemia virus-related virus in blood cells of men at risk for and infected with hiv.xenotropic murine leukemia virus-related virus has been detected in blood cells of patients with chronic fatigue syndrome and in 3.7% of healthy controls from the same geographic region. we evaluated 996 men who were participants in the multicenter aids cohort study for xenotropic murine leukemia virus-related virus sequences in blood cells by means of a real-time quantitative pcr assay. xenotropic murine leukemia virus-related virus was detected in none of the men on the basis of the absence of ...201020597166
xmrv: does this virus hold the key to myalgic encephalomyelitis/cfs?in october 2009 a team of researchers from the whittemore peterson institute, in association with the national cancer institute and the cleveland clinic in the usa, made a discovery that could potentially open the door to useful treatments for myalgic encephalomyelitis/chronic fatigue syndrome (me/cfs). the researchers, led by judy mikovits, discovered a significant correlation between me/cfs and an infectious retrovirus called xenotropic murine leukaemia virus-related virus (xmrv). xmrv is clas ...201020647985
no evidence for xmrv association in pediatric idiopathic diseases in france.retroviruses have been linked to a variety of diseases such as neoplastic and immunodeficiency disorders and neurologic and respiratory diseases. recently, a novel infectious human retrovirus, the xenotropic murine leukemia virus-related virus (xmrv), has been identified in cohorts of patients with either a familial type of prostate cancer or chronic fatigue syndrome. the apparent unrelatedness of these diseases raised the question of the potential involvement of xmrv in other diseases.here, we ...201020678193
lack of detection of xmrv in seminal plasma from hiv-1 infected men in the netherlands.xenotropic murine leukaemia virus-related virus (xmrv) is a recently discovered human gammaretrovirus with yet unknown prevalence and transmission route(s). its presence in prostate stromal fibroblasts and prostatic secretions suggests that xmrv might be sexually transmitted. we chose to study a compartment closely connected to the prostate, a location where xmrv was detected in independent studies. seminal plasma samples from hiv-1 infected men were examined as they have an increased probabilit ...201020706581
characterization of antibodies elicited by xmrv infection and development of immunoassays useful for epidemiologic studies.xenotropic murine leukemia virus-related virus (xmrv) is a human gammaretrovirus recently identified in prostate cancer tissue and in lymphocytes of patients with chronic fatigue syndrome. to establish the etiologic role of xmrv infection in human disease requires large scale epidemiologic studies. development of assays to detect xmrv-specific antibodies would greatly facilitate such studies. however, the nature and kinetics of the antibody response to xmrv infection have yet to be determined.201020716359
biology and pathophysiology of the new human retrovirus xmrv and its association with human disease.xenotropic murine leukemia virus-related virus (xmrv) is a new human retrovirus originally identified in prostate cancer patients with a deficiency in the antiviral enzyme rnase l. xmrv has been detected with varying frequencies in cases of prostate cancer and chronic fatigue syndrome (cfs), as well as in a small proportion of healthy individuals. an etiologic link between xmrv infection and human disease, however, has yet to be established. here, we summarize existing knowledge regarding the ch ...201020717743
human apobec3 proteins can inhibit xenotropic murine leukemia virus-related virus infectivity.xenotropic murine leukemia virus-related virus (xmrv) is a novel retrovirus, related to murine leukemia virus (mlv), that has been implicated in human disease. if xmrv is indeed able to replicate in humans, then one might predict that xmrv would have developed resistance to human innate antiviral resistance factors such as apobec3g (ha3g). in fact, we observed that xmrv and mlv are both highly sensitive to inhibition by ha3g and equally resistant to inhibition by murine apobec3. while several hu ...201021131013
inhibition of xenotropic murine leukemia virus-related virus by apobec3 proteins and antiviral drugs.xenotropic murine leukemia virus-related virus (xmrv), a gammaretrovirus, has been isolated from human prostate cancer tissue and from activated cd4(+) t cells and b cells of patients with chronic fatigue syndrome, suggesting an association between xmrv infection and these two diseases. since apobec3g (a3g) and apobec3f (a3f), which are potent inhibitors of murine leukemia virus and vif-deficient human immunodeficiency virus type 1 (hiv-1), are expressed in human cd4(+) t cells and b cells, we s ...201020335265
xmrv infection in patients with prostate cancer: novel serologic assay and correlation with pcr and fish.to develop a serum-based assay to detect neutralizing antibodies to the xenotropic murine leukemia virus-related virus (xmrv) retrovirus and to use this assay with polymerase chain reaction and fluorescence in situ hybridization to identify patients with prostate cancer previously exposed to xmrv infection and those who carry xmrv viral sequences in their prostate.201020371060
raltegravir is a potent inhibitor of xmrv, a virus implicated in prostate cancer and chronic fatigue syndrome.xenotropic murine leukemia-related retrovirus (xmrv) is a recently discovered retrovirus that has been linked to human prostate cancer and chronic fatigue syndrome (cfs). both diseases affect a large fraction of the world population, with prostate cancer affecting one in six men, and cfs affecting an estimated 0.4 to 1% of the population.201020376347
endogenous retroviruses as potential hazards for vaccines.retroviruses are classified as exogenous or endogenous according to their mode of transmission. generally, endogenous retroviruses (ervs) are not pathogenic in their original hosts; however, some ervs induce diseases. in humans, a novel gammaretrovirus was discovered in patients with prostate cancer or chronic fatigue syndrome. this virus was closely related to xenotropic murine leukemia virus (x-mlv) and designated as xenotropic murine leukemia virus-related virus (xmrv). the origin and transmi ...201020378372
failure to detect xenotropic murine leukaemia virus-related virus in chinese patients with chronic fatigue syndrome.recent controversy has surrounded the question of whether xenotropic murine leukaemia virus-related virus (xmrv) contributes to the pathogenesis of chronic fatigue syndrome (cfs). to investigate the question in a chinese population, 65 cfs patients and 85 blood donor controls were enrolled and multiplex real-time pcr or reverse transcriptase pcr (rt-pcr) was developed to analyze the xmrv infection status of the study participants. the assay was standardized by constructing plasmid dnas and armor ...201020836869
distribution of xenotropic murine leukemia virus-related virus (xmrv) infection in chronic fatigue syndrome and prostate cancer.in 2006, sequences described as xenotropic murine leukemia virus-related virus (xmrv) were discovered in prostate cancer patients. in october 2009, we published the first direct isolation of infectious xmrv from humans and the detection of infectious xmrv in patients with chronic fatigue syndrome. in that study, a combination of classic retroviral methods were used including: dna polymerase chain reaction and reverse transcriptase polymerase chain reaction for gag and env, full length genomic se ...201020842203
evolution of functional and sequence variants of the mammalian xpr1 receptor for mouse xenotropic gammaretroviruses and the human-derived retrovirus xmrv.genetic conflicts between retroviruses and their receptors result in the evolution of novel host entry restrictions and novel virus envelopes, and such variants can influence trans-species transmission. we screened rodents and other mammals for sequence variation in the xpr1 receptor for the mouse xenotropic or polytropic mouse leukemia viruses (x-mlvs or p-mlvs, respectively) of the gammaretrovirus family and for susceptibility to mouse-derived x/p-mlvs and to xmrv (xenotropic murine leukemia v ...201020844050
prevalence of human xenotropic murine leukemia virus-related gammaretrovirus (xmrv) in dutch prostate cancer patients.the occurrence of the retrovirus xenotropic murine leukemia virus (mlv)-related virus (xmrv) has been reported in prostate tissue of patients with prostate cancer (prca). considering the potential great medical and social relevance of this discovery, we investigated whether this finding could be confirmed in an independent group of dutch sporadic prca cases.201020878949
a cautionary tale of virus and disease.the recent identification of the gammaretrovirus xmrv and a second gammaretrovirus of a different subtype in chronic fatigue syndrome has aroused much interest, not least among sufferers. however, it remains highly controversial whether the detection of these viruses represents true infection or laboratory artifacts.201020920148
chronic controversy continues over mysterious xmrv virus. 201020689529
apobec 3g efficiently reduces infectivity of the human exogenous gammaretrovirus xmrv.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.201020668529
common inbred strains of the laboratory mouse that are susceptible to infection by mouse xenotropic gammaretroviruses and the human-derived retrovirus xmrv.laboratory mouse strains carry endogenous copies of the xenotropic mouse leukemia viruses (x-mlvs), named for their inability to infect cells of the laboratory mouse. this resistance to exogenous infection is due to a nonpermissive variant of the xpr1 gammaretrovirus receptor, a resistance that also limits in vivo expression of germ line x-mlv proviruses capable of producing infectious virus. because laboratory mice vary widely in their proviral contents and in their virus expression patterns, w ...201020943975
pcr and serology find no association between xenotropic murine leukemia virus-related virus (xmrv) and autism.abstract: xenotropic murine leukemia virus-related virus (xmrv) is a retrovirus implicated in prostate cancer and chronic fatigue syndrome (cfs). press releases have suggested that it could contribute to autism spectrum disorder (asd). in this study we used two pcr assays and one antibody assay to screen 25 blood samples from autistic children born to mothers with cfs and from 20 mixed controls including family members of the children assayed, people with fibromyalgia and people with chronic lym ...201020946639
xmrv: a new virus in prostate cancer?several recent articles have reported the presence of a gammaretrovirus, termed "xmrv" (xenotropic murine leukemia virus-related virus) in prostate cancers (pca). if confirmed, this could have enormous implications for the detection, prevention, and treatment of pca. however, other articles report failure to detect xmrv in pca. we tested nearly 800 pca samples, using a combination of real-time pcr and immunohistochemistry (ihc). the pcr reactions were simultaneously monitored for amplification o ...201020966126
prostate cancer immunology - an update for urologists.a better understanding of the immune processes in the pathogenesis and progression of prostate cancer (cap) may point the way towards improved treatment modalities. the challenge is to amplify immune responses to combat tumour escape mechanisms. infection and inflammation may have a role in prostate carcinogenesis, including the newly discovered xenotropic murine leukaemia virus (xmrv). these inflammatory states damage defence mechanisms and induce a high proliferative state favouring further mu ...201021070575
absence of detectable xenotropic murine leukemia virus-related virus in plasma or peripheral blood mononuclear cells of human immunodeficiency virus type 1-infected blood donors or individuals in africa.since the identification of xenotropic murine leukemia virus-related virus (xmrv) in prostate cancer patients in 2006 and in chronic fatigue syndrome patients in 2009, conflicting findings have been reported regarding its etiologic role in human diseases and prevalence in general populations. in this study, we screened both plasma and peripheral blood mononuclear cells (pbmncs) collected in africa from blood donors and human immunodeficiency virus type 1 (hiv-1)-infected individuals to gain evid ...201021077909
early events in retrovirus xmrv infection of the wild-derived mouse mus pahari.a novel gammaretrovirus, xenotropic murine leukemia virus-related virus (xmrv), has been identified in patients with prostate cancer and in patients with chronic fatigue syndromes. standard mus musculus laboratory mice lack a functional xpr1 receptor for xmrv and are therefore not a suitable model for the virus. in contrast, gairdner's shrew-mice (mus pahari) do express functional xpr1. to determine whether mus pahari could serve as a model for xmrv, primary mus pahari fibroblasts and mice were ...201021084477
evidence and controversies on the role of xmrv in prostate cancer and chronic fatigue syndrome.the recent discovery of xenotropic murine leukaemia virus-related virus (xmrv) in prostate cancer tissues and in the blood of individuals suffering from chronic fatigue syndrome has attracted considerable interest. however, the relevance and significance of xmrv to human disease remain unclear, since the association has not been confirmed in other studies. xmrv is the first gammaretrovirus to be found in humans. xmrv and murine leukaemia viruses share similar structures and genomic organisation. ...201021113915
the mouse "xenotropic" gammaretroviruses and their xpr1 receptor.the xenotropic/polytropic subgroup of mouse leukemia viruses (mlvs) all rely on the xpr1 receptor for entry, but these viruses vary in tropism, distribution among wild and laboratory mice, pathogenicity, strategies used for transmission, and sensitivity to host restriction factors. most, but not all, isolates have typical xenotropic or polytropic host range, and these two mlv tropism types have now been detected in humans as viral sequences or as infectious virus, termed xmrv, or xenotropic muri ...201021118532
deciphering the code for retroviral integration target site selection.upon cell invasion, retroviruses generate a dna copy of their rna genome and integrate retroviral cdna within host chromosomal dna. integration occurs throughout the host cell genome, but target site selection is not random. each subgroup of retrovirus is distinguished from the others by attraction to particular features on chromosomes. despite extensive efforts to identify host factors that interact with retrovirion components or chromosome features predictive of integration, little is known ab ...201021124862
purify first: rapid expression and purification of proteins from xmrv.purifying proteins from recombinant sources is often difficult, time-consuming, and costly. we have recently instituted a series of improvements in our protein purification pipeline that allows much more accurate choice of expression host and conditions and purification protocols. the key elements are parallel cloning, small scale parallel expression and lysate preparation, and small scale parallel protein purification. compared to analyzing expression data only, results from multiple small scal ...201021146612
detection of mlv-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors.chronic fatigue syndrome (cfs) is a serious systemic illness of unknown cause. a recent study identified dna from a xenotropic murine leukemia virus-related virus (xmrv) in peripheral blood mononuclear cells (pbmcs) from 68 of 101 patients (67%) by nested pcr, as compared with 8 of 218 (3.7%) healthy controls. however, four subsequent reports failed to detect any murine leukemia virus (mlv)-related virus gene sequences in blood of cfs patients. we examined 41 pbmc-derived dna samples from 37 pat ...201020798047
chronic fatigue syndrome. new xmrv paper looks good, skeptics admit--yet doubts linger. 201020798285
lack of infection with xmrv or other mlv-related viruses in blood, post-mortem brains and paternal gametes of autistic individuals.autistic spectrum disorder (asd) is characterized by impaired language, communication and social skills, as well as by repetitive and stereotypic patterns of behavior. many autistic subjects display a dysregulation of the immune system which is compatible with an unresolved viral infection with prenatal onset, potentially due to vertical viral transmission. recently, the xenotropic murine leukemia virus-related virus (xmrv) has been implicated in chronic fatigue syndrome (cfs) and in prostate ca ...201121373179
absence of xenotropic murine leukaemia virus-related virus in danish patients with multiple sclerosis. 201020829105
contamination of clinical specimens with mlv-encoding nucleic acids: implications for xmrv and other candidate human retroviruses.efforts to assess the prevalence of xenotropic murine leukemia virus-related virus (xmrv) in patients with prostate cancer and chronic fatigue syndrome have relied heavily on pcr-based testing of clinical samples and have yielded widely divergent findings. this week in retrovirology, reports from four independent research groups illustrate the extreme care needed to exclude dna or rna contamination in pcr analyses of xmrv. in addition, phylogenetic evidence suggesting that previously-published x ...201021171980
the xenotropic murine leukemia virus-related retrovirus debate continues at first international workshop.the 1st international workshop on xenotropic murine leukemia virus-related retrovirus (xmrv), co-sponsored by the national institutes of health, the department of health and human services and abbott diagnostics, was convened on september 7/8, 2010 on the nih campus, bethesda, md. attracting an international audience of over 200 participants, the 2-day event combined a series of plenary talks with updates on different aspects of xmrv research, addressing basic gammaretrovirus biology, host respo ...201021176195
investigation into the presence of and serological response to xmrv in cfs patients.the novel human gammaretrovirus xenotropic murine leukemia virus-related virus (xmrv), originally described in prostate cancer, has also been implicated in chronic fatigue syndrome (cfs). when later reports failed to confirm the link to cfs, they were often criticised for not using the conditions described in the original study. here, we revisit our patient cohort to investigate the xmrv status in those patients by means of the original pcr protocol which linked the virus to cfs. in addition, se ...201121408077
chronic fatigue syndrome is not caused by xmrv virus, study shows. 201021177733
detection of an infectious retrovirus, xmrv, in blood cells of patients with chronic fatigue syndrome.in october 2009, we reported the first direct isolation of infectious xenotropic murine leukemia virus-related virus (xmrv). in that study, we used a combination of biological amplification and molecular enhancement techniques to detect xmrv in more than 75% of 101 patients with chronic fatigue syndrome (cfs). since our report, controversy arose after the publication of several studies that failed to detect xmrv infection in their cfs patient populations. in this addenda, we further detail the m ...201021178474
no evidence for xmrv in german cfs and ms patients with fatigue despite the ability of the virus to infect human blood cells in vitro.xenotropic murine leukemia virus-related virus (xmrv), a novel human retrovirus originally identified in prostate cancer tissues, has recently been associated with chronic fatigue syndrome (cfs), a disabling disease of unknown etiology affecting millions of people worldwide. however, several subsequent studies failed to detect the virus in patients suffering from these illnesses or in healthy subjects. here we report the results of efforts to detect antibody responses and viral sequences in samp ...201021203514
chronic fatigue syndrome. studies point to possible contamination in xmrv findings. 201121212329
[epidemiologic and clinical characteristics of 59 persons suspecting of being infected by the hiv virus despite having repeated negative laboratory findings.]objective: to describe the epidemiologic characteristics and clinical manifestations of 59 persons recruited via an internet chat group who complained of aids-like symptoms, so as to formulate effective intervention strategies and measures. methods: case was defined as onset of any three of the following self-reported aids-like symptoms in a member of relevant "internet chat groups": persistent low grade fever, rash, swollen lymph node, fatigue, diarrhea, weight loss and low cd4(+)t count. we ad ...201021223668
xenotropic murine leukemia virus-related virus (xmrv) and blood transfusion: report of the aabb interorganizational xmrv task force. 201121235597
crystal structure of xmrv protease differs from the structures of other retropepsins.using energy and density guided rosetta refinement to improve molecular replacement, we determined the crystal structure of the protease encoded by xenotropic murine leukemia virus-related virus (xmrv). despite overall similarity of xmrv protease to other retropepsins, the topology of its dimer interface more closely resembles those of the monomeric, pepsin-like enzymes. thus, xmrv protease may represent a distinct branch of the aspartic protease family.201121258323
nf-kappab activation stimulates transcription and replication of retrovirus xmrv in human b-lineage and prostate carcinoma cells.xenotropic murine leukemia virus-related virus (xmrv) is a gammaretrovirus linked to prostate carcinoma and chronic fatigue syndrome. here we report that nf-?b activation can markedly increase xmrv production. the inflammatory cytokine tumor necrosis factor alpha (tnf-a), which activates nf-?b, significantly augmented viral gag protein production in xmrv-infected cells. reporter assays showed that tnf-a and epstein-barr virus (ebv) latent membrane protein 1 (lmp1), an intrinsic nf-?b activator, ...201121270144
primate gammaretroviruses require an ancillary factor not required for murine gammaretroviruses to infect bhk cells.bhk cells remain resistant to xenotropic murine retrovirus-related virus (xmrv) or gibbon ape leukemia virus (galv) infection, even when their respective receptors, xpr1 or pit1, are expressed. we set out to determine the stage at which viral infection is blocked and whether this block is mediated by a dominant-negative factor or the absence of a requisite ancillary factor. bhk cells bind neither xmrv nor galv envelope proteins. bhk cells expressing the appropriate receptors bind xmrv or galv en ...201121270153
no difference in antibody titers against xenotropic mlv related virus in prostate cancer cases and cancer-free controls.new elisa assays were developed to measure immunoreactivity for xmrv. antibody titers were measured in a cohort of prostate cancer cases and cancer free controls from the central united states. no statistically significant differences were observed in immunoreactivity between cases and controls for either the xmrv-env or the xmrv-gag antigen.201121281710
no xenotropic murine leukemia virus-related virus detected in fibromyalgia patients. 201121291619
evidence and controversies on the role of xmrv in prostate cancer and chronic fatigue syndrome.the recent discovery of xenotropic murine leukaemia virus-related virus (xmrv) in prostate cancer tissues and in the blood of individuals suffering from chronic fatigue syndrome has attracted considerable interest. however, the relevance and significance of xmrv to human disease remain unclear, since the association has not been confirmed in other studies. xmrv is the first gammaretrovirus to be found in humans. xmrv and murine leukaemia viruses share similar structures and genomic organisation. ...201021294212
severe restriction of xenotropic murine leukemia virus-related virus replication and spread in cultured human peripheral blood mononuclear cells.xenotropic murine leukemia virus-related virus (xmrv) is a gammaretrovirus recently isolated from human prostate cancer and peripheral blood mononuclear cells (pbmcs) of patients with chronic fatigue syndrome (cfs). we and others have shown that host restriction factors apobec3g (a3g) and apobec3f (a3f), which are expressed in human pbmcs, inhibit xmrv in transient-transfection assays involving a single cycle of viral replication. however, the recovery of infectious xmrv from human pbmcs suggest ...201121325415
infection, viral dissemination, and antibody responses of rhesus macaques exposed to the human gammaretrovirus xmrv.xenotropic murine leukemia-related virus (xmrv) was identified in association with human prostate cancer and chronic fatigue syndrome. to examine the infection potential, kinetics, and tissue distribution of xmrv in an animal model, we inoculated five macaques with xmrv intravenously. xmrv established a persistent, chronic disseminated infection, with low transient viremia and provirus in blood lymphocytes during acute infection. although undetectable in blood after about a month, xmrv viremia w ...201121325416
serologic and pcr testing of persons with chronic fatigue syndrome in the united states shows no association with xenotropic or polytropic murine leukemia virus-related viruses.in 2009, a newly discovered human retrovirus, xenotropic murine leukemia virus (mulv)-related virus (xmrv), was reported by lombardi et al. in 67% of persons from the us with chronic fatigue syndrome (cfs) by pcr detection of gag sequences. although six subsequent studies have been negative for xmrv, cfs was defined more broadly using only the cdc or oxford criteria and samples from the us were limited in geographic diversity, both potentially reducing the chances of identifying xmrv positive cf ...201121342521
xenotropic murine leukemia virus-related virus prevalence in patients with chronic fatigue syndrome or chronic immunomodulatory conditions.we investigated the prevalence of xenotropic murine leukemia virus-related virus (xmrv) among 293 participants seen at academic hospitals in boston, massachusetts. participants were recruited from the following 5 groups of patients: chronic fatigue syndrome (n = 32), human immunodeficiency virus infection (n = 43), rheumatoid arthritis (n = 97), hematopoietic stem-cell or solid organ transplant (n = 26), or a general cohort of patients presenting for medical care (n = 95). xmrv dna was not detec ...201020936980
detection of xenotropic murine leukemia virus-related virus in normal and tumor tissue of patients from the southern united states with prostate cancer is dependent on specific polymerase chain reaction conditions.there are questions regarding the prevalence of xenotropic murine leukemia virus-related virus (xmrv) in patients with prostate cancer and its association with the rnasel r462q polymorphism. we therefore investigated whether xmrv infection could be found in patients with prostate cancer from the southern united states, and we sought to verify the association with the r462q.201020936978
failure to detect xenotropic murine leukemia virus-related virus in blood of individuals at high risk of blood-borne viral infections.a xenotropic murine leukemia virus-related virus (xmrv) has recently been reported in association with prostate cancer and chronic fatigue syndrome, with a prevalence of up to 3.7% in the healthy population. we looked for xmrv in 230 patients with human immunodeficiency virus type 1 or hepatitis c infection. xmrv was undetectable in plasma or peripheral blood mononuclear cells by polymerase chain reaction targeting xmrv gag or env. t cell responses to xmrv gag were undetectable in peripheral blo ...201020936982
analysis of xmrv integration sites from human prostate cancer tissues suggests pcr contamination rather than genuine human infection.xmrv is a gammaretrovirus associated in some studies with human prostate cancer and chronic fatigue syndrome. central to the hypothesis of xmrv as a human pathogen is the description of integration sites in dna from prostate tumour tissues. here we demonstrate that 2 of 14 patient-derived sites are identical to sites cloned in the same laboratory from experimentally infected du145 cells. identical integration sites have never previously been described in any retrovirus infection. we propose that ...201121352548
mouse dna contamination in human tissue tested for xmrv.we used a pcr-based approach to study the prevalence of genetic sequences related to a gammaretrovirus, xenotropic murine leukemia virus-related virus, xmrv, in human prostate cancer. this virus has been identified in the us in prostate cancer patients and in those with chronic fatigue syndrome. however, with the exception of two patients in germany, xmrv has not been identified in prostate cancer tissue in europe. most putative associations of new or old human retroviruses with diseases have tu ...201021171966
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