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Regis A Vilchez

Publications and source records attributed to Regis A Vilchez.

At least 19 recordsLinked to original sources
PubMed2006

A prospective longitudinal study of polyomavirus shedding in lung-transplant recipients.

BACKGROUND: Polyomavirus infection causes renal dysfunction after kidney transplantation, but it has not been thoroughly investigated in nonrenal solid-organ transplantation. METHODS: Fifty lung-transplant recipients provided prospective urine and blood samples over the course of 17 months. Samples were analyzed for BK virus (BKV), JC virus (JCV), and simian virus 40 (SV40) using conventional polymerase chain reaction (PCR), sequence analysis, and quantitative real-time PCR. RESULTS: Thirty-one (62%) of 50 patients had polyomavirus detected in at least 1 urine specimen, including 16 (32%) for BKV, 12 (24%) for JCV, and 6 (12%) for SV40. Mean BKV loads (5.0 log(10) copies/mL) did not differ from those of JCV (5.7 log(10) copies/mL; P=.38), but SV40 loads (2.5 log(10) copies/mL) were lower than those of BKV (P=.006) and JCV (P=.002). Blood samples were negative. Infection with individual polyomaviruses or polyomavirus infection in aggregate was not associated with reduced creatinine clearance. Patients not shedding polyomavirus had better survival than patients shedding polyomavirus (P=.049). CONCLUSIONS: Polyomaviruses BKV and JCV were commonly detected in urine from lung-transplant recipients. SV40 was found in 12% of patients but was shed at a lower frequency and with lower viral loads than the other viruses. Polyomavirus infection was not associated with renal dysfunction.

DNA, Viral↗
PubMed2006

Simian virus 40 in posttransplant lymphoproliferative disorders.

Simian virus 40 (SV40) is an oncogenic DNA virus, which is an emergent pathogen implicated in some human malignancies, including B-cell lymphomas. As with other malignancies that occur during immunosuppression, it is hypothesized that SV40 infections may be associated with some posttransplant lymphoproliferative disorders (PTLDs). Specimens were tested initially for Epstein-Barr virus (EBV) by in situ hybridization for EBV-encoded small RNA and/or by immunohistochemical staining for EBV-latent membrane protein 1. Coded DNA specimens extracted from formalin-fixed, paraffin-embedded tissues from 22 PTLD cases were examined by polymerase chain reaction using primers for the SV40 large tumor antigen (T-ag) gene and confirmed by sequence analysis. In addition, samples were assessed for the expression of SV40 T-ag by immunohistochemical staining. Epstein-Barr virus was detected in 18 (82%) of 22 PTLD cases. Simian virus 40 T-ag sequences were detected in 2 (13%) of the 16 cases with amplifiable DNA: one with EBV-negative T-cell PTLD and the other with EBV-positive B-cell monomorphic PTLD. Immunohistochemical staining showed expression of SV40 T-ag in 1 of 2 cases containing viral DNA sequences and in none of the SV40 T-ag DNA-negative samples. Expression of SV40 T-ag was restricted to malignant cells and not to reactive lymphocytes. These results suggest that SV40 may be associated with a small subset of PTLD cases. Additional studies are needed to determine the role of SV40 in EBV-negative PTLD.

Adolescent↗
PubMed2006

Molecular and clinical perspectives of polyomaviruses: emerging evidence of importance in non-kidney transplant populations.

JC virus (JCV), BK virus (BKV) and simian virus 40 (SV40) are deoxyribonucleic acid (DNA) viruses, members of the family Polyomaviridae. These viruses establish persistent infections, and reactivate from latency in their host under immunosuppression. During the last few years there has been recognition of the morbidity related to polyomaviruses, particularly BKV in kidney transplant recipients. More importantly, recent studies indicate the potential implication of JCV, BKV, and SV40 in renal dysfunction among nonrenal organ transplant patients. Polyomaviruses are tumor-inducing viruses and animal models have provided evidence of the oncogenicity of these pathogens. Although data are not conclusive, molecular studies suggest an association of BKV and SV40 with malignancies among solid organ transplant patients. As new and potent immunosuppressive agents are introduced into clinical practice, it is believed that the incidence of polyomavirus-related diseases in organ transplantation might increase. This review evaluates the biologic and epidemiologic features of these 3 viruses, the data regarding their infections in nonkidney organ transplant patients and describes future directions in the management and research of these opportunistic pathogens.

BK Virus↗
PubMed2005

Simian virus 40 tumor antigen expression and immunophenotypic profile of AIDS-related non-Hodgkin's lymphoma.

Simian virus 40 (SV40) is associated with some systemic non-Hodgkin's lymphomas (NHL) among HIV-positive patients, based on assays for viral DNA sequences. To investigate the possible production of the viral transforming protein, we examined age-matched case-control specimens from patients with HIV/AIDS for the expression of SV40 large tumor antigen (T-ag). Masked specimens initially examined by polymerase chain reaction (PCR) for polyomavirus and herpesvirus DNA sequences were assessed for the expression of SV40 T-ag and phenotypic lymphocyte markers by immunohistochemistry (IHC). Fifty-five systemic NHL and 25 nonmalignant lymphoid and malignant nonlymphoid tissue control cases from two HIV community programs in Texas and New Jersey were scored for IHC positivity without knowledge of the PCR results. IHC showed expression of SV40 T-ag among B-cell lymphomas, whereas none of the control tissue samples were positive for T-ag (12/55, 22% vs. 0/25, 0%; P = 0.01). SV40 T-ag expression was detected only in B-cell lymphoma specimens that contained SV40 DNA sequences. Not all lymphoma cells in a positive specimen stained for T-ag, and the reaction was lower intensity than observed in SV40 hamster tumors. SV40 T-ag was demonstrated in both primary and recurrent tumors from one patient. A germinal center B-cell-like (GCB) profile was more frequently expressed by SV40-positive tumors than in Epstein-Barr virus (EBV)-related lymphomas (10/12, 83% vs. 6/13, 46%; P = 0.05), whereas a non-GCB phenotype was more frequent in EBV-positive than in SV40-positive lymphomas (7/13, 54% vs. 2/12, 17%; P = 0.05). This study shows that SV40 gene expression occurs in a fraction of cells in some B-cell lymphomas among patients with HIV/AIDS.

Adult↗
PubMed2005

Specific and quantitative detection of human polyomaviruses BKV, JCV, and SV40 by real time PCR.

BACKGROUND: The polyomaviruses that infect humans, BK virus (BKV), JC virus (JCV), and simian virus 40 (SV40), typically establish subclinical persistent infections. However, reactivation of these viruses in immunocompromised hosts is associated with renal nephropathy and hemorrhagic cystitis (HC) caused by BKV and with progressive multifocal leukoencephalopathy (PML) caused by JCV. Additionally, SV40 is associated with several types of human cancers including primary brain and bone cancers, mesotheliomas, and non-Hodgkin's lymphoma. Advancements in detection of these viruses may contribute to improved diagnosis and treatment of affected patients. OBJECTIVE: To develop sensitive and specific real time quantitative polymerase chain reaction (RQ-PCR) assays for the detection of T-antigen DNA sequences of the human polyomaviruses BKV, JCV, and SV40 using the ABI Prism 7000 Sequence Detection System. STUDY DESIGN: Assays for absolute quantification of the viral T-ag sequences were designed and the sensitivity and specificity were evaluated. A quantitative assay to measure the single copy human RNAse P gene was also developed and evaluated in order to normalize viral gene copy numbers to cell numbers. RESULTS: Quantification of the target genes is sensitive and specific over a 7 log dynamic range. Ten copies each of the viral and cellular genes are reproducibly and accurately detected. The sensitivity of detection of the RQ-PCR assays is increased 10- to 100-fold compared to conventional PCR and agarose gel protocols. The primers and probes used to detect the viral genes are specific for each virus and there is no cross reactivity within the dynamic range of the standard dilutions. The sensitivity of detection for these assays is not reduced in human cellular extracts; however, different DNA extraction protocols may affect quantification. CONCLUSION: These assays provide a technique for rapid and specific quantification of polyomavirus genomes per cell in human samples.

BK Virus↗
PubMed2005

Polyomavirus SV40 infections in Kazakhstan.

OBJECTIVES: To examine the prevalence of polyomavirus SV40 infections in Kazakhstan, a central Asian country known to have used potentially contaminated SV40 poliovaccines before 1962. METHODS: Cross-sectional study of 307 healthy volunteers from two ethnic groups (Kazakhs and Russians) in Almaty, Kazakhstan, from May through August 1999 using a specific SV40 plaque-reduction neutralization assay. RESULTS: Of the 307 volunteers enrolled in the study, 154 were Kazakhs and 153 were Russians. The overall prevalence of SV40 antibodies was 4.9%, and there was no significant difference between the ethnic groups (p = 0.7) or between males and females. The median SV40 neutralizing antibody titers in Kazakhs and Russians were 1:40 (range 1:10-1:500) and 1:20 (range 1:10-1:500), respectively. The median ages of SV40-infected Kazakhs and Russians were not different (42 vs. 24 years; p = 0.1), although there was a trend for increased seropositivity among older Kazakhs. There was no difference in SV40 positivity between those whose childhoods were spent in rural or in urban areas (p = 0.4). Importantly, 60% (9/15) of the subjects seropositive for SV40 were born from 1969 to 1980s, when poliovaccines were free from SV40. CONCLUSIONS: This study showed evidence of polyomavirus SV40 infections in Kazakhstan, not only among individuals potentially exposed to contaminated poliovaccines, but in younger people not exposed to such vaccines. As increasing evidence indicates an association of SV40 with selected types of human malignancies, prospective studies are needed to examine the risk of SV40 infection with the development of neoplasias.

Adolescent↗
PubMed2005

Plasmablastic lymphomas and plasmablastic plasma cell myelomas have nearly identical immunophenotypic profiles.

Plasmablastic lymphoma is an aggressive neoplasm that shares many cytomorphologic and immunophenotypic features with plasmablastic plasma cell myeloma. However, plasmablastic lymphoma is listed in the World Health Organization (WHO) classification as a variant of diffuse large B-cell lymphoma. To characterize the relationship between plasmablastic lymphoma and plasmablastic plasma cell myeloma, we performed immunohistochemistry using a large panel of B-cell and plasma cell markers on nine cases of plasmablastic lymphoma and seven cases of plasmablastic plasma cell myeloma with and without HIV/AIDS. The expression profiles of the tumor suppressor genes p53, p16, and p27, and the presence of Epstein-Barr virus (EBV) and human herpes virus type 8 (HHV-8) were also analyzed. All cases of plasmablastic lymphoma and plasmablastic plasma cell myeloma were positive for MUM1/IRF4, CD138, and CD38, and negative for CD20, corresponding to a plasma cell immunophenotype. PAX-5 and BCL-6 were weakly positive in 2/9 and 1/5 plasmablastic lymphomas, and negative in all plasmablastic plasma cell myelomas. Three markers that are often aberrantly expressed in cases of plasma cell myelomas, CD56, CD4 and CD10, were positive in 5/9, 2/5, and 6/9 plasmablastic lymphomas, and in 3/7, 1/5, and 2/7 plasmablastic plasma cell myelomas. A high Ki-67 proliferation index, overexpression of p53, and loss of expression of p16 and p27 were present in both tumors. No evidence of HHV-8 infection was detected in either neoplasm. The only significant difference between plasmablastic lymphoma and plasma cell myeloma was the presence of EBV-encoded RNA, which was positive in all plasmablastic lymphoma cases tested and negative in all plasma cell myelomas. In conclusion, most cases of AIDS-related plasmablastic lymphoma have an immunophenotype and tumor suppressor gene expression profile virtually identical to plasmablastic plasma cell myeloma, and unlike diffuse large B-cell lymphoma. These results do not support the suggestion in the WHO classification that plasmablastic lymphoma is a variant of diffuse large B-cell lymphoma.

Adult↗
PubMed2005

Lymphoproliferative disorders in Costa Rica and simian virus 40.

BACKGROUND AND OBJECTIVES: Simian virus 40 (SV40) is an oncogenic DNA virus implicated in some human malignancies, including lymphomas. In the present masked case-control study, we investigated the prevalence of SV40 sequences and the expression of the viral oncoprotein, large tumor antigen (T-ag), in lymphomas and control specimens from patients negative for the human immunodeficiency virus in Costa Rica. DESIGN AND METHODS: Coded specimens were anlyzed by polymerase chain reaction for SV40 and Epstein-Barr virus (EBV). SV40 sequences were confirmed by Southern blot and DNA sequence analysis. Immunohistochemistry was used to detect the expression of SV40 T-ag in coded samples and to immunophenotype the lymphomas. RESULTS: When samples were decoded, SV40 DNA sequences were detected significantly more often in lymphomas than in control samples (30/125, 24% vs. 0/91, 0%; p=0.001). SV40 DNA was detected in 26% and 10% of non-Hodgkin's and Hodgkin's lymphomas, respectively. EBV DNA was detected in 10% of lymphomas and 33% of control specimens. None of the lymphomas was positive for both SV40 and EBV. Expression of SV40 T-ag was detected in 64% of B-cell lymphomas that contained T-ag DNA sequences and in none of the samples negative for viral DNA. Not all cells in a positive tumor expressed T-ag and the reactions were relatively low intensity. A germinal center B-cell-like profile was frequently associated with SV40-positive lymphomas. Of note, 20% of patients with SV40-related lymphomas were born in the 1970s and 1980s. INTERPRETATION AND CONCLUSIONS: These results indicate that SV40 is significantly associated with some B-cell neoplasms in Costa Rica today.

Adult↗
PubMed2004

Differential ability of two simian virus 40 strains to induce malignancies in weanling hamsters.

Different strains of simian virus 40 (SV40) exist and are associated with some human malignancies, but it is not known if SV40 strains differ in biological potential in vivo. In two long-term experiments, Syrian golden hamsters 21 days of age were inoculated by the intraperitoneal route with two different strains of SV40 (10(7) plaque-forming units/animal) and were followed for 8 or 12 months. In vivo responses to strain VA45-54, isolated originally from monkey kidney cells, and to strain SVCPC, recovered from human cancers, were compared. Control animals of the same age were inoculated intraperitoneally with cell culture media. Malignancies developed only in animals infected with SV40 and not in controls. The rate of tumor development was more frequent among animals infected with strain SVCPC than with VA45-54, both in experiments held for 8 months (11/22, 50% vs. 4/20, 20%) and for 12 months (7/15, 47% vs. 3/13, 23%). Histologically, the tumors resembled mesotheliomas, osteosarcoma, and poorly differentiated sarcomas. Metastases to lung and lymph nodes occurred with both viral strains. T-antigen expression was detected in most tumor cells by immunohistochemistry. Anti-T-antigen antibodies were produced by almost all tumor-bearing animals and by about two-thirds of those that did not develop tumors after virus inoculation. SV40 viral neutralizing antibodies were detected in all tumor-bearing animals and in 92% and 38% of those inoculated with SVCPC and VA45-54, respectively, that failed to develop tumors. Antibody titers were usually higher in animals with tumors than in those without. Control animals did not develop viral antibodies. Infectious virus was recovered from 2 of 15 tumors tested. This study showed that there are biological differences between these two SV40 strains that influence the outcome of infections in normal hosts, including the development of malignancies and neutralizing antibody, and proved the principle that SV40 strains from different clades can vary in biological properties in vivo.

Animals↗
PubMed2004

Polyomavirus simian virus 40 infection associated with nephropathy in a lung-transplant recipient.

BACKGROUND: Between 1955 and 1963, millions of individuals worldwide received vaccines contaminated with polyomavirus simian virus (SV)40. Recent data suggest that some individuals may develop renal dysfunction related to SV40 infection, including individuals too young to have received contaminated vaccines. CASE REPORT AND RESULTS: Three years after bilateral lung transplantation, a 32-year-old man with cystic fibrosis developed nephrotic syndrome and progressed to end-stage renal failure over 1.5 years. He was shown to have nephropathy caused by SV40. The diagnosis was documented by detecting and confirming sequences of SV40 (but not BK or JC virus) in his kidney biopsy and urine by polymerase chain reaction, Southern blot, and DNA sequencing. Positive immunohistochemistry for SV40 was found in his kidney, and neutralizing antibodies for SV40 were detected in his serum, before and after the onset of renal dysfunction. A source for the virus was not determined. His household contacts did not have serologic or molecular evidence of SV40 infection. No serum or tissue samples were available from his 27-year-old donor. DISCUSSION: This report shows that SV40 is circulating in the community and can cause nephropathy in transplant patients.

Adult↗
PubMed2004

Emergent human pathogen simian virus 40 and its role in cancer.

The polyomavirus simian virus 40 (SV40) is a known oncogenic DNA virus which induces primary brain and bone cancers, malignant mesothelioma, and lymphomas in laboratory animals. Persuasive evidence now indicates that SV40 is causing infections in humans today and represents an emerging pathogen. A meta-analysis of molecular, pathological, and clinical data from 1,793 cancer patients indicates that there is a significant excess risk of SV40 associated with human primary brain cancers, primary bone cancers, malignant mesothelioma, and non-Hodgkin's lymphoma. Experimental data strongly suggest that SV40 may be functionally important in the development of some of those human malignancies. Therefore, the major types of tumors induced by SV40 in laboratory animals are the same as those human malignancies found to contain SV40 markers. The Institute of Medicine recently concluded that "the biological evidence is of moderate strength that SV40 exposure could lead to cancer in humans under natural conditions." This review analyzes the accumulating data that indicate that SV40 is a pathogen which has a possible etiologic role in human malignancies. Future research directions are considered.

Humans↗
PubMed2003

Epstein-Barr virus DNA loads in adult human immunodeficiency virus type 1-infected patients receiving highly active antiretroviral therapy.

Patients with human immunodeficiency virus type 1 (HIV-1) infection are at high risk of developing Epstein-Barr virus (EBV)-associated lymphoma. However, little is known of the EBV DNA loads in patients receiving highly active antiretroviral therapy (HAART). Using a real-time quantitative polymerase chain reaction assay, we demonstrated that significantly more HIV-1-infected patients receiving HAART than HIV-1-uninfected volunteers had detectable EBV DNA in blood (57 [81%] of 70 vs. 11 [16%] of 68 patients; P=.001) and saliva (55 [79%] of 68 vs. 37 [54%] of 68 patients; P=.002). The mean EBV loads in blood and saliva samples were also higher in HIV-1-infected patients than in HIV-1-uninfected volunteers (P=.001). The frequency of EBV detection in blood was associated with lower CD4+ cell counts (P=.03) among HIV-1-infected individuals, although no differences were observed in the EBV DNA loads in blood or saliva samples in the HIV-1-infected group. Additional studies are needed to determine whether EBV-specific CD4+ and CD8+ cells play a role in the pathogenesis of EBV in HIV-1-infected patients receiving HAART.

Adult↗
PubMed2003

SV40 in human brain cancers and non-Hodgkin's lymphoma.

Simian virus 40 (SV40) is a potent DNA tumor virus that is known to induce primary brain cancers and lymphomas in laboratory animals. SV40 oncogenesis is mediated by the viral large tumor antigen (T-ag), which inactivates the tumor-suppressor proteins p53 and pRb family members. During the last decade, independent studies using different molecular biology techniques have shown the presence of SV40 DNA, T-ag, or other viral markers in primary human brain cancers, and a systematic assessment of the data indicates that the virus is significantly associated with this group of human tumors. In addition, recent large independent studies showed that SV40 T-ag DNA is significantly associated with human non-Hodgkin's lymphoma (NHL). Although the prevalence of SV40 infections in humans is not known, numerous observations suggest that SV40 is a pathogen in the human population today. This review examines the molecular biology, pathology, and clinical data implicating SV40 in the pathogenesis of primary human brain cancers and NHL and discusses future research directions needed to define a possible etiologic role for SV40 in these malignancies.

Amino Acid Sequence↗
PubMed2003

Simian virus 40 in human cancers.

BACKGROUND: Many studies have reported the presence of simian virus 40 (SV40) deoxyribonucleic acid (DNA) or protein in human brain tumors and bone cancers, malignant mesothelioma, and non-Hodgkin's lymphoma. However, the small samples and lack of control groups in some reports have made it difficult to assess their reliability. METHODS: Studies were included in this analysis if they met the following criteria: original studies of patients with primary brain tumors and bone cancers, malignant mesothelioma, or non-Hodgkin's lymphoma; the investigation of SV40 was performed on primary cancer specimens; the analysis included a control group; and the same technique was used for cases and controls. Included reports were published from 1975 to 2002. RESULTS: Thirteen studies fulfilled the criteria for the investigation of primary brain cancers (661 tumors and 482 control samples). Specimens from patients with brain tumors were almost four times more likely to have evidence of SV40 infection than were those from controls (odds ratio [OR] = 3.9; 95% confidence interval [CI]: 2.6 to 5.8). The association was even stronger for mesothelioma (OR = 17; 95% CI: 10 to 28; based on 15 studies with 528 mesothelioma samples and 468 control samples) and for bone cancer (OR = 25; 95% CI: 6.8 to 88; based on four studies with 303 cancers and 121 control samples). SV40 DNA was also more frequent in samples from patients with non-Hodgkin's lymphoma (OR = 5.4; 95% CI: 3.1 to 9.3; based on three studies with 301 cases and 578 control samples) than from controls. CONCLUSION: These results establish that SV40 is associated significantly with brain tumors, bone cancers, malignant mesothelioma, and non-Hodgkin's lymphoma. Studies are needed to assess current prevalence of SV40 infections.

Blotting, Southern↗