Systemic BK Virus Infection in a Pediatric Patient With Severe Combined Immunodeficiency.

Human BK virus (BKV) infection is known to occur mostly during childhood with the establishment of latent infection with no tissue damage or clinical manifestations. However, conditions causing immunosuppression can lead to increased virus replication and tissue damage. Although the tissues most commonly involved are the kidneys, bladder, ureters and, to some extent, brain tissue, there are some reports that suggest that BKV may cause multisystemic infections. In this case, a 12-month-old child was seen to suffer from multiple gastrointestinal infections. This prompted a search for immunodeficiencies, which revealed the presence of severe combined immunodeficiency. The child was eventually hospitalized and continued showing recurrent bouts of gastroenteritis as well as lower respiratory infection. After multiple antibiotic courses, he developed acute kidney injury, a hemophagocytic syndrome, and eventually respiratory failure, which led to his death a year later. Autopsy findings revealed the presence of a disseminated BKV infection involving the kidneys, ureters, leptomeninges, and pancreas. Analysis of the literature failed to show any previous case of BKV pancreatitis. The present case suggests that BKV can damage more tissues than previously reported and may be responsible for systemic infections in immunosuppressed patients.

Effect of polyoma viremia on 3-year allograft kidney function.

BACKGROUND: Polyoma viremia is associated with damage to renal tubular and urothelial cells. This may imply that a certain level of viremia, even cleared thereafter, could be associated with long-term renal dysfunction. METHODS: We, retrospectively, analyzed 390 first renal transplants adult recipients (≥18 years) who were monitored for BK viremia in the first 12 months and evaluated estimated GFR (MDRD-4 equation) at 1 month and at the last follow-up (959 ± 392 days). RESULTS: One hundred and ninety-nine patients (51%) developed at least one positive viremia: 105 (53%) low viremia (<104  copies/mL), 36 (18%) high viremia (4 × 104  > viremia ≥ 104  copies/mL) and 58 (15%) viremia (≥4 × 104  copies/mL) consistent with polyoma virus associated nephropathy (PyVAN). Out of these 58 patients, 24 (6%) developed bx-proven (SV40+) PyVAN and 34(8.7%) presumptive PyVAN (SV40-). Baseline characteristics, immunosuppression, KDRI, rejection episodes, etc., did not differ among groups but there were more deceased donors and ATG induction therapy in the high viremia group. At last follow-up, all patients in the low, high viremia and presumptive PyVAN (except 2) had cleared BK viremia. Bx-proven PyVAN led to 14 graft losses, 10 due to PyVAN. In the presumptive PyVAN there was only one graft loss registered as due to PyVAN. eGFR, at 1 month after KTx, did not differ among groups (51 ± 22 vs 48 ± 24 vs 45 ± 27 vs 43 ± 18 vs 46 ± 22 mL/min/1.73 m2 ), for no, low and high viremia as well for presumptive PyVAN and bx-proven PyVAN groups, respectively. At the last follow-up, eGFR did not differ between the no, low, and high viremia compared to baseline and to each other but was statistically lower in the presumptive and bx-proven PyVAN (38 ± 15 and 17 ± 7 mL/min/1.73 m2 ) either compared to baseline or to the other groups. CONCLUSIONS: This study shows that low and high levels of BK viremia do not lead to GFR changes although very high viremia levels, compatible with presumptive or bx-proven PyVAN, even if cleared thereafter, lead to allograft damage and decreased GFR.

Investigation of three oncogenic epitheliotropic viruses shows human papillomavirus in association with non-melanoma skin cancer.

Non-melanoma skin cancers (NMSC) share similar risk factors with other virus-related cancers, despite the lack of proved causal association between viral infection and NMSC development. We investigated the presence of Merkel cell polyomavirus (MCPyV), Epstein-Barr virus (EBV), and human papillomavirus (HPV) DNA in 83 NMSC fresh-frozen and 16 non-cancerous skin biopsies and evaluated viral infection according to demographical data, histopathological diagnosis, and ultraviolet exposure. Our results showed that 75% of NMSC biopsies were positive for at least one out of three viruses, whereas only 38% of non-cancerous skin biopsies were positive (p = 0.02). Notably, HPV detection was frequent in NMSC (43%) and nearly absent (one sample, 6.7%) in non-cancerous biopsies (p = 0.007). MCPyV was associated with sites of higher exposure to ultraviolet radiation (p = 0.010), while EBV was associated with a compromised immune system (p = 0.032). Our study showed that HPV was strongly associated with NMSC while EBV and MCPyV with other risk factors. Though further studies are required to elucidate the role of viral infection in NMSC development and management, this study supports the possible role of oncogenic viruses in skin cancers, especially HPV.

Cerebellar cortical degeneration associated with feline leukemia virus infection and cerebellar lymphoma in a young cat.

Background: Cerebellar cortical degeneration (CCD) is the premature death of cerebellar neurons of heterogeneous etiology that is uncommonly observed as a neurological complication of certain neoplasia. Case Description: Here, we report an 8-month-old male domestic cat with altered consciousness, symmetric ataxia, hypermetric gait, vertical positional nystagmus, mydriasis, strabismus, intention tremor of the head, and increased patellar reflexes. Neuroanatomical diagnosis suggested a multifocal brain dysfunction (cerebellar and cerebral). The cat tested seropositive for feline leukemia virus. Cerebrospinal fluid analysis indicated mononuclear and neutrophilic pleocytosis. Contrast computed tomography imaging revealed multiple hypodense heterogeneous areas in both cerebral hemispheres, mild ventriculomegaly at the level of the caudal fossa, and a circular sharply marginated, homogeneously hyperdense mass occupying the right cerebellar hemisphere. Postmortem study indicated a 1.1 × 1.3 × 1.2 cm mass in the right cerebellar hemisphere close to the vermis. Histopathological analysis showed diffuse and severe Purkinje cell loss with a decrease in granular cell density and moderate gliosis compatible with CCD. Further, numerous neoplastic lymphoid cells were observed in the infiltrated mass, consistent with a diagnosis of central nervous system (CNS) lymphoma. Immunohistochemistry showed CD20 expression, indicative of a B-cell immunophenotype. In humans, CCD is reported as a rare paraneoplastic syndrome in patients with Hodgkin lymphoma. CNS lymphoma and/or Feline Leukemia Virus (FeLV) infection were both considered as a possible cause of CCD in this case. Conclusion: This is the first described case of possible paraneoplastic cerebellar cortical degeneration associated with CNS lymphoma and/or FeLV infection in a domestic cat.

Determination of viremia cut-off for risk to develop BKPyV-associated nephropathy among kidney transplant recipients.

BACKGROUND: BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) is a consequence of BKPyV replication in the urinary tract in kidney transplant recipients (KTR). OBJECTIVES: The objectives were to determine the prevalence of BKPyV replication and BKPyVAN, risk factors associated to sustained viremia and BKPyVAN, and viremia cut-off that best predict the occurrence of sustained viremia and nephropathy in KTR of a single University Hospital Kidney Transplant Center. PATIENTS AND METHODS: All KTR undergoing transplantation from August 2010 to December 2011 were enrolled and monitored up to 2 years posttransplantation for BKPyV viruria by decoy cells shedding or polymerase chain reaction (PCR) and viremia by PCR. Kidney biopsy was indicated if sustained viremia (two or more viremia above 10 000 copies/mL) to confirm BKPyVAN diagnosis. RESULTS: In this study, 326 transplants were performed and 246 patients were included. Prevalence of viruria was 36.9%, viremia 22.3% and nephropathy 3.2%. Male gender was the only risk factor associated to sustained viremia or nephropathy. Cut-off value of viremia that best discriminates the progression to sustained viremia and to BKPyVAN was 37 488 and 44 956 copies/mL, respectively. CONCLUSIONS: Prevalence of viruria, viremia, and nephropathy were similar to those reported in literature but the cut-off value of viremia that best discriminates the risk of progression to nephropathy was greater than the value usually reported, which is 10 000 copies/mL.

Putative progressive and abortive feline leukemia virus infection outcomes in captive jaguarundis (Puma yagouaroundi).

BACKGROUND: Feline leukemia virus (FeLV) is an exogenous gammaretrovirus of domestic cats (Felis catus) and some wild felids. The outcomes of FeLV infection in domestic cats vary according to host susceptibility, virus strain, and infectious challenge dose. Jaguarundis (Puma yagouaroundi) are small wild felids from South and Central America. We previously reported on FeLV infections in jaguarundis. We hypothesized here that the outcomes of FeLV infection in P. yagouaroundi mimic those observed in domestic cats. The aim of this study was to investigate the population of jaguarundis at Fundação Parque Zoológico de São Paulo for natural FeLV infection and resulting outcomes. METHODS: We investigated the jaguarundis using serological and molecular methods and monitored them for FeLV-related diseases for 5 years. We retrieved relevant biological and clinical information for the entire population of 23 jaguarundis held at zoo. Post-mortem findings from necropsies were recorded and histopathological and immunohistopathological analyses were performed. Sequencing and phylogenetic analyses were performed for FeLV-positive samples. For sample prevalence, 95% confidence intervals (CI) were calculated. Fisher's exact test was used to compare frequencies between infected and uninfected animals. P-values <0.05 were considered significant. RESULTS: In total, we detected evidence of FeLV exposure in four out of 23 animals (17%; 95% CI 5-39%). No endogenous FeLV (enFeLV) sequences were detected. An intestinal B-cell lymphoma in one jaguarundi was not associated with FeLV. Two jaguarundis presented FeLV test results consistent with an abortive FeLV infection with seroconversion, and two other jaguarundis had results consistent with a progressive infection and potentially FeLV-associated clinical disorders and post-mortem changes. Phylogenetic analysis of env revealed the presence of FeLV-A, a common origin of the virus in both animals (100% identity) and the closest similarity to FeLV-FAIDS and FeLV-3281 (98.4% identity), originally isolated from cats in the USA. CONCLUSIONS: We found evidence of progressive and abortive FeLV infection outcomes in jaguarundis, and domestic cats were probably the source of infection in these jaguarundis.

Chelonid herpesvirus 5 in secretions and tumor tissues from green turtles (Chelonia mydas) from Southeastern Brazil: A ten-year study.

Fibropapillomatosis (FP), a neoplastic disease characterized by the formation of multiple tumors affecting different species of sea turtles and, most often, the green turtle (Chelonia mydas), is considered one of the major threats to the survival of this species. Recent studies indicate that Chelonid herpesvirus (ChHV5) is the etiological agent of this disease, though its association with anthropogenically altered environments and the immune status of these animals also appears to contribute to disease expression and tumor formation. In this study, tumor biopsy and secretions from green turtles captured off the coast of São Paulo State, Brazil, were used in histological and molecular analyses to detect and characterize circulating ChHV5. In 40.9% of cases, the tumor histopathological findings revealed focal ballooning degeneration with intranuclear inclusion bodies, results which are suggestive of viral infection. ChHV5 was detected using polymerase chain reaction (PCR) on the animals' skin, ocular tumor biopsies, and ocular and oral secretions. The analysis of the detected ChHV5 sequences revealed two distinct genetic sequences together. Phylogenetic analysis indicated that Brazilian samples were similar to ChHV5 samples described for the Atlantic phylogeographic group and are therefore part of the same clade as the Gulf of Guinea and Puerto Rico samples. This similarity suggests a possible flow of the virus between these three regions.

Evidence of regression of fibropapillomas in juvenile green turtles Chelonia mydas caught in Niterói, southeast Brazil.

Fibropapillomatosis is a disease characterized by cutaneous tumors affecting all marine turtle species, but mostly Chelonia mydas. The disease was first reported in 1938, and since then, the number of sightings has been increasing over the years. This disease can cause many complications in the affected animal and can lead to death, and is thus included in the many threats to marine turtle populations. It is still not known for certain what causes this disease, although many studies indicate a herpesvirus as the main etiologic agent. The incidence of fibropapillomatosis is rarely reported in adults, leading to speculations that there may be a cure for the disease or that the animals die before reaching adulthood. In this paper, 2 cases of fibropapillomatosis regression are reported from juvenile C. mydas caught between July 2008 and July 2010 in the coastal zone of Itaipu, Niterói, Rio de Janeiro, Brazil. These individuals were identified photographically upon recapture. One individual had a total regression (disappearance) of external papilloma within 164 d between first capture and recapture, and the other individual had a partial regression (decrease in size) observed within 13 to 188 d of recapture. The mechanism that triggers the regression is still unknown but is likely to be an immune system response or removal of the tumor promoter. There are few reported cases of regression in the world, and constant monitoring through mark-recapture is necessary to assess whether the marine turtles affected by this disease have real chances of survival.

Mouse mammary tumor virus-like gene sequences are present in lung patient specimens.

BACKGROUND: Previous studies have reported on the presence of Murine Mammary Tumor Virus (MMTV)-like gene sequences in human cancer tissue specimens. Here, we search for MMTV-like gene sequences in lung diseases including carcinomas specimens from a Mexican population. This study was based on our previous study reporting that the INER51 lung cancer cell line, from a pleural effusion of a Mexican patient, contains MMTV-like env gene sequences. RESULTS: The MMTV-like env gene sequences have been detected in three out of 18 specimens studied, by PCR using a specific set of MMTV-like primers. The three identified MMTV-like gene sequences, which were assigned as INER6, HZ101, and HZ14, were 99%, 98%, and 97% homologous, respectively, as compared to GenBank sequence accession number AY161347. The INER6 and HZ-101 samples were isolated from lung cancer specimens, and the HZ-14 was isolated from an acute inflammatory lung infiltrate sample. Two of the env sequences exhibited disruption of the reading frame due to mutations. CONCLUSION: In summary, we identified the presence of MMTV-like gene sequences in 2 out of 11 (18%) of the lung carcinomas and 1 out of 7 (14%) of acute inflamatory lung infiltrate specimens studied of a Mexican Population.

Identification of viral infections in the prostate and evaluation of their association with cancer.

BACKGROUND: 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-XMRV viruses have not been reported. We assessed associations between prostate cancer, prostate viral infections, and the RNASEL 462Q allele in Mexican cancer patients and controls. METHODS: 130 subjects (55 prostate cancer cases and 75 controls) were enrolled in the study. DNA and RNA isolated from prostate tissues were screened for the presence of viral genomes. Genotyping of the RNASEL R462Q variant was performed by Taqman method. RESULTS: R/R, R/Q, and Q/Q frequencies for R462Q were 0.62, 0.38, and 0.0 for PC cases and 0.69, 0.24, and 0.07 for controls, respectively. HPV sequences were detected in 11 (20.0%) cases and 4 (5.3%) controls. XMRV and HCMV infections were detected in one and six control samples, respectively. The risk of PC was significantly increased (Odds Ratio = 3.98; 95% CI: 1.17-13.56, p = 0.027) by infection of the prostatic tissue with HPV. BKV, JCV, and SV40 sequences were not detected in any of the tissue samples examined. CONCLUSIONS: We report a positive association between PC and HPV infection. The 462Q/Q RNASEL genotype was not represented in our PC cases; thus, its interaction with prostate viral infections and cancer could not be evaluated.

Detection of polyomavirus major capsid antigen (VP-1) in human pilomatricomas.

The family Polyomaviridae is composed of small, non-enveloped, double-stranded DNA viruses widely used to study cell transformation in vitro and tumor induction in vivo. The development of pilomatricomas in mice experimentally infected with polyomavirus led us to detect the viral major capsid protein VP-1 in human pilomatricomas. This tumor, even uncommon, is one of the most frequent benign hair follicle tumors in humans and is composed of proliferating matrix cells that undergo keratinization, and form cystic neoplasms. The detection of VP-1 was performed using the peroxidase-antiperoxidase technique in paraffin-embedded slides with a specific primary serum. Adjacent slides treated with normal rabbit serum as a primary were employed as internal control. Positive and negative controls were also employed as well as slides of lesions caused by human papillomavirus to rule out any unspecific cross-reactivity. In 4 out of 10 cases polyomavirus VP-1 was clearly detected in nuclei of human pilomatricomas proliferating cells, in a patchy pattern of distribution. The controls confirmed the specificity of the immunocytochemical procedure. These results could indicate either an eventual infection of the virus in already developed tumors or alternatively, a direct involvement of polyomavirus in the pathogenesis of some pilomatricomas. The recent discovery of a new human polyomavirus associated with Merkel cell carcinomas has been a strong contribution to better understand the pathogenesis of some human uncommon skin cancers. Hopefully the results reported in this work will encourage further research on the role of polyomavirus in other human skin neoplasms.

Penile squamous cell carcinoma: anatomic, pathologic and viral studies in Paraguay (1993-2007).

In developed countries, penile squamous cell carcinoma (SCC) account for < 1% of all malignancies in men. It is more frequent in rural populations of Africa, Asia and Latin America, where it may constitute nearly 10% of all carcinomas. In Paraguay, approximately 30-40 new cases are diagnosed per year. Different subtypes of penile carcinomas have been described. Most SCCs are of the usual type (60%). Less frequent variants include basaloid (10%), warty (10%), papillary (15%), verrucous (3%), sarcomatoid (4%) and adenosquamous (1%). Mixed forms also exist. Because there is a correlation between histologic subtype and biologic behavior, accurate subtyping is important. The prevalence of human papillomavirus (HPV) in invasive SCC is approximately 42%, with a strong association of HPV and basaloid and warty variants. Among the most important prognostic factors are histologic grade and depth of invasion. It is important for surgical pathologists to know the anatomy of the penis and possible routes of tumor spread because negative resection margins are crucial to avoid local recurrences. The most frequently involved margins are the urethra and periurethral tissues, including Buck's fascia. Probable precursor lesions of penile carcinoma include squamous hyperplasia, low and high grade squamous intraepithelial neoplasia and lichen sclerosus.

EBV+ lymphoepithelial carcinoma of the parotid gland in Mexican Mestizo patients with chronic autoimmune diseases.

Lymphoepithelial carcinomas of the salivary gland are rare tumors constantly associated with Epstein-Barr virus (EBV) and mainly identified in Asiatic and Greenlander population. Four cases have been described in Caucasians, only two with EBV infection. We describe two cases of parotid gland lymphoepithelial carcinomas in Mexican mestizo women in which chronic latent EBV infection was documented by immunohistochemistry and in situ hybridization. One patient had primary Sjögren's syndrome and the other systemic lupus erythematosus of six and three years of evolution, respectively. Epithelial neoplastic cells showed latency pattern II (LMP1+, EBNA-2-, EBER+) with a dense inflammatory infiltrate composed mainly by CD8+ T lymphocytes. Follow-up excluded nasopharyngeal involvement in both patients. This report expands the ethnic groups in which salivary lymphoepithelial carcinomas associated with chronic latent EBV infection have been described, and illustrates for the first time its association with autoimmune diseases in two women living in a region non-endemic for this unusual neoplasm.

Immunolocalization of the Epstein-Barr nuclear antigen-1 in conjunctival squamous carcinomas and dysplasias.

Epstein-Barr virus (EBV) has been linked etiologically to infectious mononucleosis, some non-Hodgkin as well as Hodgkin lymphomas, and lymphoepithelioma-like carcinomas. Moreover, various EBV antigens have been identified by a variety of techniques in a number of visceral carcinomas including breast, prostate, colon and lung primaries. We have now demonstrated by immunohistochemistry the presence of EBV nuclear antigen-1 (EBNA-1) in 4 of 15 cases of conjuntival squamous carcinomas and related dysplasias. At present, there is no significant evidence linking etiologically EVB to this type of tumor and dysplasia. However, our findings merit further investigation given the growing evidence that EBV may enhance proliferation and aggressiveness of tumor systems as well as the immortalization of non-neoplastic cells.

Differential expression of the human homologue of drosophila discs large oncosuppressor in histologic samples from human papillomavirus-associated lesions as a marker for progression to malignancy.

High-risk HPVs play a causal role in the development of cervical cancer, and their E6 oncoproteins target h-Dlg for ubiquitin-mediated proteolysis. The h-Dlg oncosuppressor is associated with cell-cell interactions, and deregulation of these structures leads to defective cell adhesion, loss of cell polarity and unregulated proliferation. We evaluated the contribution of this E6 activity in the progression to malignancy in HPV infections by analyzing h-Dlg expression in HPV-associated lesions. We analyzed h-Dlg in cervical, laryngeal, vulvar, colon and kidney histologic samples by Dlg immunohistochemistry. HPV association was ascertained by a PCR-colorimetric method. Although Dlg was certainly expressed in intraepithelial cervical, vulvar and laryngeal HPV-associated lesions, its cellular and tissue distribution patterns were altered compared to normal tissue. However, marked reduction in Dlg levels was observed in HPV-positive invasive cervical carcinomas. To elucidate whether the loss of Dlg was significant for carcinogenesis in general, we investigated Dlg expression in tumors not associated with HPV. In colon and kidney carcinomas, Dlg was expressed, albeit with a different pattern of distribution with respect to the normal tissue. The loss of Dlg may be considered a late-stage marker in cervical carcinogenesis, but alterations in its expression and localization take place during the different dysplastic stages. Dlg downregulation and/or alterations in its localization may contribute to transformation and may explain some of the characteristics of the malignant cells, such as loss of polarity and high migration ability.

[The paradox of polyomaviruses. Lytic infection or tumor induction?]. / La dicotomía de los virus polioma. Infección lítica o inducción de neoplasias?

Murine polyomaviruses can produce lytic infections in mouse cell cultures or transform in vitro rat fibroblasts through a complex interaction with key cellular regulators. After infection of newborn mice, some strains of polyomavirus induce epithelial and mesenchymal tumors. It has been described that there is a direct relationship between viral dissemination in the mouse and tumor induction. However, at a single cell level lytic infection and transformation would not be able to coexist. The existence of 3 distinct cell populations in polyoma-induced tumors, classified according to the presence or absence of viral DNA and viral capsid protein VP-1 have been described. We have reported a fourth type of cell in the neoplasms, that can express the early and the late viral genes but do not allow virus assembly, probably due to underphosphorylation of VP-1. The mechanisms of polyoma intracellular migration and dissemination in the mouse are discussed, related to the virus' ability of tumor induction.

Human papillomavirus cervical infection in Guarani Indians from the rainforest of Misiones, Argentina.

OBJECTIVE: To evaluate the prevalence of human papillomavirus (HPV) cervical infection in women from the South American Guarani Indian tribe located in the rain forest of Misiones, north-eastern Argentina; a region with a high incidence of cervical carcinoma. METHODS: A cross-sectional cytological and HPV screening of sexually active Guarani women from nine Indian settlements was conducted. Demographic data, information about sexual behavior, and gynaecological history were recorded. Fresh cervical specimens from 239 patients were collected, of which 207 were included in this study. Cytology and microbiological detection were carried out by the Papanicolaou and Gram stain methods, respectively. HPV detection and typing were analyzed by PCR and RFLP. RESULTS: Pap smears in 96% of all patients showed an inflammatory pattern. A possible etiologic agent was found in 58% of cases: 52% Trichomonas vaginalis, 35% Gardnerella vaginalis and 13% Candida sp. Seven cases had cytological changes compatible with Low Grade Intraepithelial Lesion (LGSIL), one with High Grade Intraepithelial Lesion (HGSIL) and one in situ cervical cancer. The prevalence for generic HPV infection was 64% (133/207). Genotyping gave a 26% prevalence for HPV types 16/18, 13% for types 6/11 and 30% for other types, with nine mixed infections. CONCLUSION: This work reports for the first time the prevalence of cervical HPV infection in Guarani women. Nearly all Guarani women had some grade of cervical disease. Generic HPV infection prevalence was elevated (64%), with predominance of high risk types 16/18. A large variety of viral types was detected, including high to intermediate risk types not found previously in the region.

La dicotomia de los virus polioma: infeccion litica o induccion de neoplasias? / The paradox of polyomaviruses: lytic infection or tumor induction?

Los virus Polioma murinos provocan infecciones líticas en cultivos de células de ratón y transforman in vitro células de rata a través de la interacción de su oncogén mT con diversos reguladores celulares. Luego de su inoculación en ratones neonatos inducen neoplasias epiteliales y mesenquimáticas. Se ha propuestoque las cepas de polioma más oncogénicas son aquellas que previamente replican más en el ratón. Sin embargo, a nivel de una sola célula la infección lítica y la transformación deberían ser mutuamente excluyentes.En cada neoplasia han sido descriptos 3 tipos celulares según expresen el DNA viral solo o concomitantementecon la proteína mayor de la cápside VP1, o que no contengan DNA viral ni VP-1. En nuestro laboratorio detectamos la existencia de un cuarto tipo celular en las neoplasias, en el que se expresa la totalidad del genoma viral pero no ocurre el ensamblaje, probablemente por alteraciones en la fosforilación de VP-1. Se discuten los mecanismos de migración intracelular de Polioma, la diseminación en el ratón y los factores que podrían estarinvolucrados en la inducción de neoplasias o en la infección lítica inducidas por el virus.

La dicotomia de los virus polioma: infeccion litica o induccion de neoplasias? / The paradox of polyomaviruses: lytic infection or tumor induction?

Los virus Polioma murinos provocan infecciones líticas en cultivos de células de ratón y transforman in vitro células de rata a través de la interacción de su oncogén mT con diversos reguladores celulares. Luego de su inoculación en ratones neonatos inducen neoplasias epiteliales y mesenquimáticas. Se ha propuestoque las cepas de polioma más oncogénicas son aquellas que previamente replican más en el ratón. Sin embargo, a nivel de una sola célula la infección lítica y la transformación deberían ser mutuamente excluyentes.En cada neoplasia han sido descriptos 3 tipos celulares según expresen el DNA viral solo o concomitantementecon la proteína mayor de la cápside VP1, o que no contengan DNA viral ni VP-1. En nuestro laboratorio detectamos la existencia de un cuarto tipo celular en las neoplasias, en el que se expresa la totalidad del genoma viral pero no ocurre el ensamblaje, probablemente por alteraciones en la fosforilación de VP-1. Se discuten los mecanismos de migración intracelular de Polioma, la diseminación en el ratón y los factores que podrían estarinvolucrados en la inducción de neoplasias o en la infección lítica inducidas por el virus. (AU)