RESUMO
BACKGROUND: 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. METHODS: Prostate tissue specimens of 144 patients with prostate cancer from the southern United States were genotyped for R462Q by real time polymerase chain reaction allelic discrimination and were screened for XMRV proviral DNA by nested polymerase chain reaction specific for the env gene. RESULTS: The R462Q polymorphism was found at an allelic frequency of 0.33. XMRV was detected in 32 (22%) of the 144 patients. Patients were significantly more likely to test positive for XMRV in both tumor and normal tissue rather than either alone (κ = 0.64). A positive result for XMRV was not significantly correlated with the R462Q polymorphism (P = .82) or clinical pathological parameters of prostate cancer, including Gleason score (P = .29). CONCLUSIONS: XMRV is detectable in normal and tumor prostate tissue from patients with prostate cancer, independent of R462Q. The presence of XMRV in normal tissue suggests that infection may precede cancer onset.
Assuntos
Vírus da Leucemia Murina/isolamento & purificação , Reação em Cadeia da Polimerase , Próstata/virologia , Neoplasias da Próstata/virologia , Provírus/isolamento & purificação , Infecções por Retroviridae/virologia , Infecções Tumorais por Vírus/virologia , Alelos , Sequência de Aminoácidos , Estudos de Coortes , Endorribonucleases/genética , Frequência do Gene , Predisposição Genética para Doença , Humanos , Vírus da Leucemia Murina/genética , Masculino , Dados de Sequência Molecular , Polimorfismo Genético , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/genética , Provírus/genética , Estudos Retrospectivos , Infecções por Retroviridae/epidemiologia , Alinhamento de Sequência , Infecções Tumorais por Vírus/epidemiologia , Estados Unidos/epidemiologia , Proteínas do Envelope Viral/genéticaRESUMO
BACKGROUND: Xenotropic murine leukemia virus-related virus (XMRV) has been found in the prostatic tissue of prostate cancer patients and in the blood of chronic fatigue syndrome patients. However, numerous studies have found little to no trace of XMRV in different human cohorts. Based on evidence suggesting common transmission routes between XMRV and HIV-1, HIV-1 infected individuals may represent a high-risk group for XMRV infection and spread. METHODOLOGY/PRINCIPAL FINDINGS: DNA was isolated from the peripheral blood mononuclear cells (PBMCs) of 179 HIV-1 infected treatment naïve patients, 86 of which were coinfected with HCV, and 54 healthy blood donors. DNA was screened for XMRV provirus with two sensitive, published PCR assays targeting XMRV gag and env and one sensitive, published nested PCR assay targeting env. Detection of XMRV was confirmed by DNA sequencing. One of the 179 HIV-1 infected patients tested positive for gag by non-nested PCR whereas the two other assays did not detect XMRV in any specimen. All healthy blood donors were negative for XMRV proviral sequences. Sera from 23 HIV-1 infected patients (15 HCV(+)) and 12 healthy donors were screened for the presence of XMRV-reactive antibodies by Western blot. Thirteen sera (57%) from HIV-1(+) patients and 6 sera (50%) from healthy donors showed reactivity to XMRV-infected cell lysate. CONCLUSIONS/SIGNIFICANCE: The virtual absence of XMRV in PBMCs suggests that XMRV is not associated with HIV-1 infected or HIV-1/HCV coinfected patients, or blood donors. Although we noted isolated incidents of serum reactivity to XMRV, we are unable to verify the antibodies as XMRV specific.