RESUMO
Bovine polyomavirus-1 (BoPyV-1, Epsilonpolyomavirus bovis) is widespread in cattle and has been detected in commercialized beef at supermarkets in the USA and Germany. BoPyV-1 has been questioned as a probable zoonotic agent with documented increase in seropositivity in people exposed to cattle. However, to date, BoPyV-1 has not been causally associated with pathology or disease in any animal species, including humans. Here we describe and illustrate pathological findings in an aborted bovine fetus naturally infected with BoPyV-1, providing evidence of its pathogenicity and probable abortigenic potential. Our results indicate that: (i) BoPyV-1 can cause severe kidney lesions in cattle, including tubulointerstitial nephritis with cytopathic changes and necrosis in tubular epithelial cells, tubular and interstitial inflammation, and interstitial fibroplasia; (ii) lesions are at least partly attributable to active viral replication in renal tubular epithelial cells, which have abundant intranuclear viral inclusions; (iii) BoPyV-1 large T (LT) antigen, resulting from early viral gene expression, can be detected in infected renal tubular epithelial cells using a monoclonal antibody raised against Simian Virus-40 polyomavirus LT antigen; and (iv) there is productive BoPyV-1 replication and virion assembly in the nuclei of renal tubular epithelial cells, as demonstrated by the ultrastructural observation of abundant arrays of viral particles with typical polyomavirus morphology. Altogether, these lesions resemble the "cytopathic-inflammatory pathology pattern" proposed in the pathogenesis of Human polyomavirus-1-associated nephropathy in immunocompromised people and kidney allograft recipients. Additionally, we sequenced the complete genome of the BoPyV-1 infecting the fetus, which represents the first whole genome of a BoPyV-1 from the Southern Hemisphere. Lastly, the BoPyV-1 strain infecting this fetus was isolated, causing a cytopathic effect in Madin-Darby bovine kidney cells. We conclude that BoPyV-1 is pathogenic to the bovine fetus under natural circumstances. Further insights into the epidemiology, biology, clinical relevance, and zoonotic potential of BoPyV-1 are needed.
Assuntos
Transplante de Rim , Nefrite Intersticial , Infecções por Polyomavirus , Polyomavirus , Infecções Tumorais por Vírus , Animais , Anticorpos Monoclonais , Antígenos Virais de Tumores , Bovinos , Feto/patologia , Humanos , Rim , Transplante de Rim/efeitos adversos , Nefrite Intersticial/complicações , Nefrite Intersticial/patologia , Infecções por Polyomavirus/complicações , Vírus 40 dos Símios , Infecções Tumorais por Vírus/complicaçõesRESUMO
BACKGROUND: BK polyomavirus-associated nephropathy (PyVAN) is an important complication after kidney transplantation. Prevalence ranges from 1% to 10%, and graft loss occurs in approximately 50% of the cases. There is no effective treatment, so early viral detection with immunosuppression tapering is the current strategy to prevent PyVAN. AIMS: To verify the frequency of PyVAN in a single center and evaluate the response to immunosuppressive adjustments through graft survival analysis. METHODS: Retrospective evaluation of a cohort of kidney transplant recipients with biopsy-proven PyVAN, compared with no-PyVAN patients regarding clinical aspects, immunosuppression, and graft survival over at least 2 years. RESULTS: There were 1404 kidney transplants analyzed in the study period, 58 with biopsy-proven PyVAN. Cumulative incidence was 4.1%. Median time from transplantation to PyVAN diagnosis was 6 (1-41) months. PyVAN was associated with recipient male gender (P = .041) and deceased donation (P = .005). Graft survival was inferior for PyVAN compared to no-PyVAN patients, 81.8% vs 75.2%, P = .019. Thirteen (22.4%) PyVAN patients lost their grafts, nine (15.5%) losses attributed to BKPyV infection. Three patients with BKPyV-associated graft losses were submitted to a successful second kidney transplant, with no evidence of viral replication during follow-up. CONCLUSION: PyVAN still is an important cause of kidney graft failure. Even though implementing active vigilance and immunosuppressive adjustment, this real-life single-center study demonstrated inferior graft survival in PyVAN patients compared to non-PyVAN.
Assuntos
Rejeição de Enxerto/virologia , Nefropatias/virologia , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/etiologia , Infecções Tumorais por Vírus/etiologia , Adulto , Vírus BK/patogenicidade , Feminino , Sobrevivência de Enxerto , Humanos , Terapia de Imunossupressão/efeitos adversos , Rim/patologia , Rim/virologia , Nefropatias/prevenção & controle , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/complicações , Estudos Retrospectivos , Fatores Sexuais , Transplante Homólogo/efeitos adversos , Infecções Tumorais por Vírus/complicações , Viremia , Adulto JovemRESUMO
The BK virus (BKV) produces a subclinical kidney infection in immunocompetent individuals. However, viremia may occur in kidney transplant patients with ongoing immunosuppression. BKV-associated nephropathy (BKVN) has no specific treatment and is a leading cause of organ transplant loss. In this study, we evaluated the predisposition and the clinical impact of BKV replication in kidney transplant patients during post-transplant monitoring in a reference institution in Brazil. Demographic, clinical and laboratory data generated during routine outpatient follow-up were retrospectively collected. BK viremia was investigated using real-time polymerase chain reaction. Of the 553 participants, 7.4% (n = 41) presented BKV replication. Of these, 16 (39%) lost their kidney graft and interstitial nephritis was identified on kidney biopsy in 50% of the cases. Among the evaluated variables, only the use of the immunosuppressant mycophenolate sodium was identified as a risk factor for viremia (OR 7.96; 95% CI 2.35 to 26.98). The graft survival estimate in BKV-positive patients was significantly reduced (24.8% vs. 85.6%) after 10 years of transplantation. We concluded that defining predisposing factors remains an important challenge for the prevention and control of BKV activity following kidney transplantation, especially considering the development of BKVN and its strong effect on graft maintenance.
Assuntos
Vírus BK/fisiologia , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/complicações , Infecções Tumorais por Vírus/complicações , Viremia/complicações , Replicação Viral/imunologia , Adulto , Estudos Transversais , Feminino , Rejeição de Enxerto , Humanos , Masculino , Infecções por Polyomavirus/virologia , Estudos Retrospectivos , Fatores de Risco , Infecções Tumorais por Vírus/virologia , Viremia/virologiaRESUMO
ABSTRACT The BK virus (BKV) produces a subclinical kidney infection in immunocompetent individuals. However, viremia may occur in kidney transplant patients with ongoing immunosuppression. BKV-associated nephropathy (BKVN) has no specific treatment and is a leading cause of organ transplant loss. In this study, we evaluated the predisposition and the clinical impact of BKV replication in kidney transplant patients during post-transplant monitoring in a reference institution in Brazil. Demographic, clinical and laboratory data generated during routine outpatient follow-up were retrospectively collected. BK viremia was investigated using real-time polymerase chain reaction. Of the 553 participants, 7.4% (n = 41) presented BKV replication. Of these, 16 (39%) lost their kidney graft and interstitial nephritis was identified on kidney biopsy in 50% of the cases. Among the evaluated variables, only the use of the immunosuppressant mycophenolate sodium was identified as a risk factor for viremia (OR 7.96; 95% CI 2.35 to 26.98). The graft survival estimate in BKV-positive patients was significantly reduced (24.8% vs. 85.6%) after 10 years of transplantation. We concluded that defining predisposing factors remains an important challenge for the prevention and control of BKV activity following kidney transplantation, especially considering the development of BKVN and its strong effect on graft maintenance.
Assuntos
Humanos , Masculino , Feminino , Adulto , Infecções Tumorais por Vírus/complicações , Viremia/complicações , Replicação Viral/imunologia , Transplante de Rim/efeitos adversos , Vírus BK/fisiologia , Infecções por Polyomavirus/complicações , Infecções Tumorais por Vírus/virologia , Viremia/virologia , Estudos Transversais , Estudos Retrospectivos , Fatores de Risco , Infecções por Polyomavirus/virologia , Rejeição de EnxertoRESUMO
Infection with polyomavirus (BK virus) is the cause of renal graft losses in more than 50% of the infected cases. There should be a high index of suspicion about this disease, although the incidence is only between 2% and 5% as the future of renal graft depends on the early and appropriate management of the same. Herein, we describe three clinical cases: Two were those of kidney transplant and the third, a combined kidney-pancreas transplant. In these cases, by reducing immunosuppression and, in one case, replacing the calcineurin inhibitor by MTOR (mammalian target of rapamycin) in addition, we were able to preserve of the normal function of the transplanted organs.
Assuntos
Vírus BK , Imunossupressores/efeitos adversos , Necrose do Córtex Renal/virologia , Transplante de Rim/efeitos adversos , Infecções por Polyomavirus/complicações , Infecções Tumorais por Vírus/complicações , Adulto , Feminino , Sobrevivência de Enxerto , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Transplante de Pâncreas/efeitos adversosRESUMO
BACKGROUND: Breast cancer is a complex multifactorial genetic disease. Among other factors, race and, to an even greater extent, viruses are known to influence the development of this heterogeneous disease. It has been reported that MMTV-like (HMTV) gene sequences with a 90 to 98% homology to mouse mammary tumor virus are found in several populations with a prevalence range of 0 to 74%. In the Mexican population, 4.2% of patients with breast cancer exhibit the presence of HMTV (MMTV-like) sequences. The aim of this study was to evaluate the presence and current prevalence of retroviral HMTV (MMTV-like) sequences in breast cancer in Mexican women. METHODS: We used nested PCR and real-time PCR with a TaqMan probe. As a positive control, we used the C3H MMTV strain inserted into pBR322 plasmid. To confirm that we had identified the HMTV sequences, we sequenced the amplicons and compared these sequences with those of MMTV and HMTV (GenBank AF033807 and AF346816). RESULTS: A total of 12.4% of breast tumors were HMTV-positive, and 15.7% of the unaffected tissue samples from 458 patients were HMTV-positive. A total of 8.3% of the patients had both HMTV-positive tumor and adjacent tissues. The HMTV-positive samples presented 98% similarity to the reported HMTV sequence. CONCLUSIONS: These results confirm that the HMTV sequence is present in breast tumors and non-affected tissues in the Mexican population. HMTV should be considered a prominent causative agent of breast cancer.
Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Vírus do Tumor Mamário do Camundongo , Infecções por Retroviridae/complicações , Infecções Tumorais por Vírus/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Neoplasias da Mama/patologia , Estudos Transversais , DNA Viral , Feminino , Produtos do Gene env/genética , Humanos , Glândulas Mamárias Humanas/virologia , Vírus do Tumor Mamário do Camundongo/classificação , Vírus do Tumor Mamário do Camundongo/genética , México/epidemiologia , Camundongos , Pessoa de Meia-Idade , Filogenia , Prevalência , Estudos Prospectivos , Infecções por Retroviridae/virologia , Infecções Tumorais por Vírus/virologiaRESUMO
BACKGROUND: HIV infection leads to a decreasing immune response, thereby facilitating the appearance of other infections, one of the most important ones being HPV. However, studies are needed for determining associations between immunodeficiency caused by HIV and/or the presence of HPV during the course of cervical lesions and their degree of malignancy. This study describes the cytological findings revealed by the Papanicolaou test, laboratory characteristics and HPV molecular profile in women with and without HIV infection. METHODS: A total of 216 HIV-positive and 1,159 HIV-negative women were invited to participate in the study; PCR was used for the molecular detection of HPV in cervical samples. Statistical analysis (such as percentages, Chi-square test and Fisher's exact test when applicable) determined human papillomavirus (HPV) infection frequency (single and multiple) and the distribution of six types of high-risk-HPV in women with and without HIV infection. Likewise, a logistic regression model was run to evaluate the relationship between HIV-HPV infection and different risk factors. RESULTS: An association was found between the frequency of HPV infection and infection involving 2 or more HPV types (also known as multiple HPV infection) in HIV-positive women (69.0% and 54.2%, respectively); such frequency was greater than that found in HIV-negative women (44.3% and 22.7%, respectively). Statistically significant differences were observed between both groups (p = 0.001) regarding HPV presence (both in infection and multiple HPV infection). HPV-16 was the most prevalent type in the population being studied (p = 0.001); other viral types had variable distribution in both groups (HIV-positive and HIV-negative). HPV detection was associated with <500 cell/mm(3) CD4-count (p = 0.004) and higher HIV-viral-load (p = 0.001). HPV-DNA detection, <200 cell/mm(3) CD4-count (p = 0.001), and higher HIV-viral-load (p = 0.001) were associated with abnormal cytological findings. CONCLUSIONS: The HIV-1 positive population in this study had high multiple HPV infection prevalence. The results for this population group also suggested a greater association between HPV-DNA presence and cytological findings. HPV detection, together with low CD4 count, could represent useful tools for identifying HIV-positive women at risk of developing cervical lesions.
Assuntos
Coinfecção/epidemiologia , Infecções por HIV/epidemiologia , Infecções por Papillomavirus/epidemiologia , Adolescente , Adulto , Idoso , Alphapapillomavirus/classificação , Alphapapillomavirus/genética , Contagem de Linfócito CD4 , Colômbia/epidemiologia , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/genética , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Prevalência , Fatores de Risco , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/epidemiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Carga Viral , Adulto JovemRESUMO
Breast cancer is the most frequent malignancy affecting women worldwide. It has been suggested that infection by Epstein Barr Virus (EBV), Mouse Mammary Tumor Virus or a similar virus, MMTV-like virus (MMTV-LV), play a role in the etiology of the disease. However, studies looking at the presence of these viruses in breast cancer have produced conflicting results, and this possible association remains controversial. Here, we used polymerase chain reaction assay to screen specific sequences of EBV and MMTV-LV in 86 tumor and 65 adjacent tissues from Mexican women with breast cancer. Neither tumor samples nor adjacent tissue were positive for either virus in a first round PCR and only 4 tumor samples were EBV positive by a more sensitive nested PCR. Considering the study's statistical power, these results do not support the involvement of EBV and MMTV-LV in the etiology of breast cancer.
Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Herpesvirus Humano 4 , Vírus do Tumor Mamário do Camundongo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Neoplasias da Mama/diagnóstico , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Feminino , Herpesvirus Humano 4/genética , Humanos , Vírus do Tumor Mamário do Camundongo/genética , Programas de Rastreamento , México/epidemiologia , Camundongos , Pessoa de Meia-Idade , Vigilância da População , Infecções por Retroviridae/complicações , Infecções por Retroviridae/virologia , Infecções Tumorais por Vírus/complicações , Infecções Tumorais por Vírus/virologiaRESUMO
This study evaluated the relative occurrences of BK virus (BKV) and JC virus (JCV) infections in patients with chronic kidney disease (CKD). Urine samples were analysed from CKD patients and from 99 patients without CKD as a control. A total of 100 urine samples were analysed from the experimental (CKD patients) group and 99 from the control group. Following DNA extraction, polymerase chain reaction (PCR) was used to amplify a 173 bp region of the gene encoding the T antigen of the BKV and JCV. JCV and BKV infections were differentiated based on the enzymatic digestion of the amplified products using BamHI endonuclease. The results indicated that none of the patients in either group was infected with the BKV, whereas 11.1% (11/99) of the control group subjects and 4% (4/100) of the kidney patients were infected with the JCV. High levels of urea in the excreted urine, low urinary cellularity, reduced bladder washout and a delay in analysing the samples may have contributed to the low prevalence of infection. The results indicate that there is a need to increase the sensitivity of assays used to detect viruses in patients with CDK, especially given that polyomavirus infections, especially BKV, can lead to a loss of kidney function following transplantation.
Assuntos
Vírus BK/isolamento & purificação , Vírus JC/isolamento & purificação , Falência Renal Crônica/complicações , Infecções por Polyomavirus/diagnóstico , Infecções Tumorais por Vírus/diagnóstico , Adulto , Idoso , Estudos de Casos e Controles , DNA Viral/análise , Feminino , Humanos , Falência Renal Crônica/urina , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Infecções por Polyomavirus/complicações , Infecções Tumorais por Vírus/complicações , Adulto JovemRESUMO
This study evaluated the relative occurrences of BK virus (BKV) and JC virus (JCV) infections in patients with chronic kidney disease (CKD). Urine samples were analysed from CKD patients and from 99 patients without CKD as a control. A total of 100 urine samples were analysed from the experimental (CKD patients) group and 99 from the control group. Following DNA extraction, polymerase chain reaction (PCR) was used to amplify a 173 bp region of the gene encoding the T antigen of the BKV and JCV. JCV and BKV infections were differentiated based on the enzymatic digestion of the amplified products using BamHI endonuclease. The results indicated that none of the patients in either group was infected with the BKV, whereas 11.1% (11/99) of the control group subjects and 4% (4/100) of the kidney patients were infected with the JCV. High levels of urea in the excreted urine, low urinary cellularity, reduced bladder washout and a delay in analysing the samples may have contributed to the low prevalence of infection. The results indicate that there is a need to increase the sensitivity of assays used to detect viruses in patients with CDK, especially given that polyomavirus infections, especially BKV, can lead to a loss of kidney function following transplantation.