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At least 19 recordsLinked to original sources
PubMed2003

The use of virus-like particles for gene transfer.

A major challenge in the field of gene therapy is the development of new carrier/delivery systems that lack the disadvantages of current transfer systems. In the past, some time has been spent developing such modified or alternative vectors. A new candidate is represented by virus-like particles (VLPs). It has been shown that recombinant expression of the major structural proteins of many viruses leads to the formation of VLPs. Such VLPs exhibit morphology similar to the empty capsids of the virus from which they are derived. VLPs are non-infectious, have a similar tropism to the natural virus, and show comparable cellular uptake and intracellular trafficking. Since its discovery, VLP technology has gained importance in biomedical research. Although most investigations into VLP technology have dealt with vaccine development, some research groups have demonstrated that VLPs could also represent a useful gene therapy delivery system. This review will focus on studies performed with VLPs from members of the Papillomaviridae and Polyomaviridae families.

Animals↗
PubMed2005

Distribution, characterization and significance of polyomavirus genomic sequences in tumors of the brain and its covering.

The etiology of brain tumors and meningiomas is still unknown. Several factors have been considered, such as genetic predisposition and environmental risk factors, but the hypothesis that one or more infectious agents may play a role in tumor pathogenesis has also been investigated. Therefore, emphasis was placed on the neurooncogenic family Polyomaviridae and the presence of human polyomavirus DNA sequences and JCV mRNA were examined in malignant human brain biopsies. Italian patients affected with different types of neoplasias of the brain and its covering were enrolled. The patients underwent surgical tumor excision and the presence of the polyomavirus genome in biopsy and other body fluids was evaluated by PCR. In addition, the genomic organization of JCV was examined in depth, with the aim of providing information on genotype distribution and TCR rearrangements in the population affected with intracranial neoplasms. On the whole, polyomavirus DNA was found in 50% of the biopsy specimens studied, JC virus DNA and BK virus DNA were amplified in 40.6% mainly glioblastomas and 9.4% of the tissue specimens, respectively, while none of the biopsy specimens tested contained Simian virus 40 DNA. Genotype 1 and Mad 4 TCR organization were the most frequent in the population enrolled. Although a cause and effect was not demonstrated and the specific role of the viruses remains unknown, the findings appear to confirm the hypothesis that JCV and BKV could be important co-factors in tumor pathogenesis.

Adult↗
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↗
PubMedDate not supplied

JC virus genotyping offers a new paradigm in the study of human populations.

A small DNA virus, named JC virus (JCV) and belonging to the Polyomaviridae, is attracting the attention of anthropologists worldwide, as JCV genotyping appears to be a novel means of elucidating human migrations and the origins of various ethnic groups. The basic properties of JCV, the regional distributions of JCV genotypes, and the phylogenetic relationships among various JCV genotypes are described. Then, a study is described in which the origin of the modern Japanese was extensively investigated using the JCV genotyping method. Based on JCV genotypes in neighboring areas, the origins of people who carried JCV genotypes to the Japanese Archipelago are discussed. Finally, the relationships between JCV genotypes and Y-chromosome haplogroups are examined, as genetic variation on the Y chromosome has recently been examined in detail to investigate ancient human migrations and the population structures of human groups.

Chromosomes, Human, Y↗
PubMed2006

Progressive multifocal leukoencephalopathy in a haploidentical stem cell transplant recipient: a clinical, neuroradiological and virological response after treatment with risperidone.

JC virus (JCV) is a double-stranded DNA virus belonging to family Polyomaviridae. It causes progressive multifocal leukoencephalopathy (PML), mainly in immunosuppressed people. JCV had been shown to require the serotonin 2A receptor for host cell entry. We report a case of clinical, neuroradiological and virological response of biopsy-proven PML in a 33-year-old comatose woman after treatment with the anti-psychotic drug risperidone. Since risperidone is the tightest binding of current drugs to this receptor we think this may have blocked JCV entry in our patient, allowing her immune recovery and viral clearance.

Adult↗
PubMed2003

Detection of infectious bovine polyomavirus.

Bovine polyomavirus (BPyV) is a member of the Polyomaviridae, a virus that was originally thought to be of simian origin but was later shown to be of bovine origin, the primate cultures having been contaminated through the use of foetal bovine serum. The significance of this agent to the biotechnology industry cannot be underestimated. The presence of BPyV in serum batches poses a serious risk for the contamination of human therapeutic products. The current PCR based assays provide a means of detecting virus sequences but give no indication as to the infectious nature of the virus. The communication reports the successful development of an assay to detect infectious BPyV using an in vitro amplification system followed by PCR. A lengthy culture period on bovine cells was required before replicating BPyV could be detected and distinguished from non-replicating virus in the cell culture supernatant. A mock-test assay using foetal bovine serum positive for BPyV showed that there was no evidence of replicating BPyV in the serum sample. The BPyV spiked serum control showed that replicating virus was present thus confirming that the serum itself did not inhibit replication of the virus. Cells harvested during the culture period were subjected to fixation, embedding and sectioning and examined by electron microscopy. Intact virus-like particles of approximately 40-50nm were observed in the nucleus of the bovine kidney cells, the site of polyomavirus replication.

Animals↗
PubMed1993

Coevolution of persistently infecting small DNA viruses and their hosts linked to host-interactive regulatory domains.

Although most RNA viral genomes (and related cellular retroposons) can evolve at rates a millionfold greater than that of their host genomes, some of the small DNA viruses (polyomaviruses and papillomaviruses) appear to evolve at much slower rates. These DNA viruses generally cause host species-specific inapparent primary infections followed by life-long, benign persistent infections. Using global progressive sequence alignments for kidney-specific Polyomaviridae (mouse, hamster, primate, human), we have constructed parsimonious evolutionary trees for the viral capsid proteins (VP1, VP2/VP3) and the large tumor (T) antigen. We show that these three coding sequences can yield phylogenetic trees similar to each other and to that of their host species. Such virus-host "co-speciation" appears incongruent with some prevailing views of viral evolution, and we suggest that inapparent persistent infections may link virus and most host evolution. Similarity analysis identified three specific regions of polyoma regulatory gene products (T antigens) as highly conserved, and two of these regions correspond to binding sites for host regulatory proteins (p53, the retinoblastoma gene product p105, and the related protein p107). The p53 site overlaps with a conserved ATPase domain and the retinoblastoma site corresponds to conserved region 1 of E1A protein of adenovirus type 5. We examined the local conservation of these binding sequences and show that the conserved retinoblastoma binding domain is characteristic and inclusive of the entire polyomavirus family, but the conserved p53-like binding domain is characteristic and inclusive of three entire families of small DNA viruses: polyomaviruses, papillomaviruses, and parvoviruses. The evolution of small-DNA-virus families may thus be tightly linked to host evolution and speciation by interaction with a subset of host regulatory proteins.

Amino Acid Sequence↗
PubMed2004

Pathology of spontaneous and experimental infections by Goose haemorrhagic polyomavirus.

Haemorrhagic nephritis enteritis of geese (HNEG) is a fatal disease of geese aged from 3 to 12 weeks. The causative virus, Goose haemorrhagic polyomavirus (GHPV), is a member of the Polyomaviridae family We examined goslings either spontaneously or experimentally infected with GHPV. Tissues were sampled for histology, GHPV DNA detection and electron microscopy. Clinical signs and gross lesions observed in experimentally infected goslings were largely consistent with those noticed in field cases. Histological examination showed that, in the acute phase of HNEG, GHPV replicates in almost all the tissues with a particular tropism for endothelial and lymphoid cells. Haemorrhagic foci were widespread in many tissues, including brain. Ultrastructural features were largely consistent with other polyomavirus infections, with accumulation of virions in the nucleus. Non-typical, double-membraned organelles were observed in the cytoplasm. GHPV DNA distribution was widespread in tissues of infected birds, from day 5 post-infection. GHPV therefore induces a systemic disease in its host, leading to severe vascular dysfunction and immunosuppressive B-cell depletion.

Animals↗
PubMed2001

Analysis of minimal sequences on JC virus VP1 required for capsid assembly.

Human JC virus (JCV) belongs to the family of Polyomaviridae. The viral capsid is composed of 72 capsomeres. Five VP1 molecules make up a capsomere structure. To investigate the minimal sequences on JCV VP1 polypeptide required for capsid assembly, the first 12 (Delta N12) and 19 (Delta N19) amino acids at the N-terminus and the last 16 (Delta C16), 17 (Delta C17), and 31 (Delta C31) amino acids at the C-terminus of VP1 were truncated and expressed in E. coli. The VP1 proteins of Delta N12 and Delta C16 were able to self-assemble into a virus-like particle similar to that of wild-type (WT) VP1. However, the mutant proteins of Delta N19, Delta C17, and Delta C31 formed a pentameric capsomere structure as demonstrated by a 10-50% sucrose gradient centrifugation and electron microscopy. These results suggest that the 12 amino-terminal and 16 carboxy-terminal amino acids of VP1 are dispensable for the formation of virus-like particles, and further truncation at either end of VP1 leads to the loss of this property.

Capsid↗
PubMed2006

Update on BK virus entry and intracellular trafficking.

BK virus (BKV) is a small, non-enveloped, double-stranded DNA virus and a member of the Polyomaviridae family. As the recently recognized etiologic agent of polyomavirus-associated nephropathy, the events involved in BKV invasion of host cells are an important area of study. Using cell culture models, the mechanism by which BKV infects permissive hosts to gain access to the replication machinery within these cells is beginning to unfold. BKV uses an N-linked glycoprotein containing an alpha(2,3)-linked sialic acid as a receptor. After this initial attachment, BKV enters cells through caveolae-mediated endocytosis. Intracellular trafficking via cellular cytoskeletal components follows this relatively slow and cholesterol-dependent internalization. BKV must reach the nucleus for viral transcription and replication to occur. Elucidating the steps of the early viral lifecycle would provide clues to help explain the infectious spread and pathology of this human pathogen.

Animals↗
PubMed2006

Identification of human and animal adenoviruses and polyomaviruses for determination of sources of fecal contamination in the environment.

The Adenoviridae and Polyomaviridae families comprise a wide diversity of viruses which may be excreted for long periods in feces or urine. In this study, a preliminary analysis of the prevalence in the environment and the potential usefulness as source-tracking tools of human and animal adenoviruses and polyomaviruses has been developed. Molecular assays based on PCR specifically targeting human adenoviruses (HAdV), porcine adenoviruses (PAdV), bovine adenoviruses (BAdV), and bovine polyomaviruses (BPyV) were applied to environmental samples including urban sewage, slaughterhouse, and river water samples. PAdV and BPyV were detected in a very high percentage of samples potentially affected by either porcine or bovine fecal contamination, respectively. However, BAdV were detected in only one sample, showing a lower prevalence than BPyV in the wastewater samples analyzed. The 22 slaughterhouse samples with fecal contamination of animal origin showed negative results for the presence of HAdV. The river water samples analyzed were positive for the presence of both human and animal adenoviruses and polyomaviruses, indicating the existence of diverse sources of contamination. The identities of the viruses detected were confirmed by analyses of the amplified sequences. All BPyV isolates showed a 97% similarity in nucleotide sequences. This is the first time that PAdV5, BAdV6, and BPyV have been reported to occur in environmental samples. Human and porcine adenoviruses and human and bovine polyomaviruses are proposed as tools for evaluating the presence of viral contamination and for tracking the origin of fecal/urine contamination in environmental samples.

Abattoirs↗
PubMed2006

New commercially available PCR and microplate hybridization assay for detection and differentiation of human polyomaviruses JC and BK in cerebrospinal fluid, serum, and urine samples.

JC and BK human polyomaviruses (family Polyomaviridae) may cause severe neurological or urinary tract pathologies in immunocompromised hosts. In the present study, we evaluated a new commercially available PCR and microplate colorimetric hybridization assay for the standardized differential detection of JC virus (JCV) and BK virus (BKV) genomes in clinical samples. This JC/BK Consensus test was first evaluated by testing serial dilutions of JCV or BKV plasmid DNA standards and was then compared with an in-house reference PCR assay for the detection of JC and BK virus genomes in 70 cerebrospinal fluid (CSF) samples of patients with neurological disorders and in 75 serum or plasma samples and 125 urine samples of renal graft recipients. This new test allowed a limit of detection of 10 copies and 1 copy of JC and BK virus genomes, respectively, and was able to differentiate various levels of JCV, BKV, and mixed JCV and BKV DNA genomes in a single reaction tube. Our results showed 100% specificity and sensitivity for the JC/BK Consensus test with CSF samples. With serum or plasma samples, this test had a sensitivity and a specificity of 100% for both JCV and mixed JCV and BKV DNA detection and a sensitivity and a specificity of 100 and 97.8% for BKV DNA detection, respectively. With urine samples, the sensitivity and specificity were 100 and 96.6%, respectively, for JCV DNA detection; 100 and 89.4%, respectively, for BKV DNA detection; and 44.4 and 100%, respectively, for mixed JCV and BKV DNA detection. In conclusion, our data indicate that this new test, the JC/BK Consensus test, is valuable for the sensitive and specific differential detection of single JCV and BKV infections in CSF, serum or plasma, and urine samples. The use of this reliable PCR assay would improve the routine virological diagnosis as well as the clinical care of immunocompromised patients with polyomavirus-related pathologies.

Adult↗
PubMed2006

Comparing phylogenetic codivergence between polyomaviruses and their hosts.

Seventy-two full genomes corresponding to nine mammalian (67 strains) and two avian (5 strains) polyomavirus species were analyzed using maximum likelihood and Bayesian methods of phylogenetic inference. Our fully resolved and well-supported (bootstrap proportions > 90%; posterior probabilities = 1.0) trees separate the bird polyomaviruses (avian polyomavirus and goose hemorrhagic polyomavirus) from the mammalian polyomaviruses, which supports the idea of spitting the genus into two subgenera. Such a split is also consistent with the different viral life strategies of each group. Simian (simian virus 40, simian agent 12 [Sa12], and lymphotropic polyomavirus) and rodent (hamster polyomavirus, mouse polyomavirus, and murine pneumotropic polyomavirus [MPtV]) polyomaviruses did not form monophyletic groups. Using our best hypothesis of polyomavirus evolutionary relationships and established host phylogenies, we performed a cophylogenetic reconciliation analysis of codivergence. Our analyses generated six optimal cophylogenetic scenarios of coevolution, including 12 codivergence events (P < 0.01), suggesting that Polyomaviridae coevolved with their avian and mammal hosts. As individual lineages, our analyses showed evidence of host switching in four terminal branches leading to MPtV, bovine polyomavirus, Sa12, and BK virus, suggesting a combination of vertical and horizontal transfer in the evolutionary history of the polyomaviruses.

Animals↗
PubMed2005

Complete nucleotide sequence of polyomavirus SA12.

The Polyomaviridae have small icosahedral virions that contain a genome of approximately 5,000 bp of circular double-stranded DNA. Polyomaviruses infect hosts ranging from humans to birds, and some members of this family induce tumors in test animals or in their natural hosts. We report the complete nucleotide sequence of simian agent 12 (SA12), whose natural host is thought to be Papio ursinus, the chacma baboon. The 5,230-bp genome has a genetic organization typical of polyomaviruses. Sequences encoding large T antigen, small t antigen, agnoprotein, and the viral capsid proteins VP1, VP2, and VP3 are present in the expected locations. We show that, like its close relative simian virus 40 (SV40), SA12 expresses microRNAs that are encoded by the late DNA strand overlapping the 3' end of large T antigen coding sequences. Based on sequence comparisons, SA12 is most closely related to BK virus (BKV), a human polyomavirus. We have developed a real-time PCR test that distinguishes SA12 from BKV and the other closely related polyomaviruses JC virus and SV40. The close relationship between SA12 and BKV raises the possibility that these viruses circulate between human and baboon hosts.

Amino Acid Sequence↗
PubMed1977

Progressive multifocal leukoencephalopathy. A cause of visual loss.

A patient had been treated for chronic lymphocytic leukemia for five years before developing visual blurring as the manifestation of occipital lobe lesions of progressive multifocal leukoencephalopathy (PML). The disease is caused by an infection of the CNS oligodendrocytes by a papovavirus, whose replication is facilitated by an impairment of the host's cell-mediated immunologic system. The multiplying virus destroys the oligodendrocytes and causes extensive demyelination of the white matter of the brain. Antiviral agents, such as cytarabine, may be beneficial in treating patients with PML.

Cytarabine↗
PubMed1976

Epidermodysplasia verruciformis.

Epidermodysplasia verruciformis (EV) is characterized by the early onset of extensive, persistent verruca plana that may undergo malignant transformation. Immunologic studies of a case of EV confirmed by electron microscopic identification of the virus disclosed no detectable abnormalities. The importance of this uncommon clinical syndrome lies in its demonstration that benign papovavirus, the etiologic agent of warts, can produce malignant neoplasms in genetically susceptible hosts.

Antibodies, Viral↗