The human polyomavirus, JCV, causes the fatal demyelinating disease progressive multifocal leukoencephalopathy in immunocompromised patients. We found that serotonergic receptor 5HT2AR could act as cellular for JCV on glial cells. 5HT2A antagonists inhibited infection, and monoclonal antibodies directed at receptors blocked infection of cells by but not SV40. Transfection receptor-negative HeLa with a rescued virus this was antibody to receptor. A tagged colocalized labeled an endosomal...

JC polyomavirus (JCPyV) is a ubiquitous human pathogen that causes progressive multifocal leukoencephalopathy (PML), severe and often fatal neurodegenerative disease in immunocompromised or immunomodulated patients. The mechanisms responsible for initiating infection susceptible cells are not completely known. major attachment receptor the virus, lactoseries tetrasaccharide c (LSTc), paradoxically expressed on oligodendrocytes astrocytes brain, virus does bind to these cells. Because cell...

The human polyomavirus, JCPyV, is the causative agent of progressive multifocal leukoencephalopathy (PML) in immunosuppressed and immunomodulated patients. Initial infection with JCPyV common virus establishes a long-term persistent urogenital system 50–70% population worldwide. A major gap field that we do not know how traffics from periphery to brain cause disease. Our recent discovery choroid plexus epithelial cells are fully susceptible together reports vivo has led us hypothesize plays...

Abstract Malignant pleural mesothelioma (MPM) is a rapidly fatal disease whose diagnosis, particularly through less invasive techniques such as analysis of effusion, can be challenging. Currently, commercially available diagnostic test based on microRNA (miRNA) expression patterns purported to distinguish between and lung adenocarcinoma. Yet, the biological basis this technology has not been reported in literature, little research aimed at determining how differential miRNA contributes...

The human JC polyomavirus (JCPyV) causes the rapidly progressing demyelinating disease progressive multifocal leukoencephalopathy (PML). occurs most often in individuals with AIDS but also receiving immunomodulatory therapies for immune-related diseases such as multiple sclerosis. JCPyV infection of host cells requires pentasaccharide lactoseries tetrasaccharide c (LSTc) and serotonin receptor 5-hydroxytryptamine (5-HT) 5-HT2AR. While LSTc is involved initial attachment virus to via...

Polyomaviruses are ubiquitous pathogens that cause severe disease in immunocompromised individuals. JC polyomavirus (JCPyV) is the causative agent of fatal demyelinating progressive multifocal leukoencephalopathy (PML), whereas BK (BKPyV) causes polyomavirus-induced nephropathy and hemorrhagic cystitis. Vaccines or antiviral therapies targeting these viruses do not exist, treatments focus on reducing underlying immunosuppression. We demonstrate retro-2(cycl), an inhibitor ricin Shiga-like...

ABSTRACT The human JC polyomavirus (JCPyV) establishes an asymptomatic, persistent infection in the kidneys of majority population and is causative agent fatal demyelinating disease progressive multifocal leukoencephalopathy (PML) immunosuppressed individuals. Mad-1 strain JCPyV, a brain isolate, was shown earlier to require α2,6-linked sialic acid on lactoseries tetrasaccharide c (LSTc) glycan for attachment host cells. In contrast, JCPyV kidney isolate type 3 strain, WT3, has been reported...

ABSTRACT The human JC polyomavirus (JCPyV) is the causative agent of fatal, demyelinating disease progressive multifocal leukoencephalopathy (PML). Mad-1 prototype strain JCPyV uses glycan lactoseries tetrasaccharide c (LSTc) and serotonin receptor 5-HT 2A to attach enter into host cells, respectively. Specific residues in viral capsid protein VP1 are responsible for direct interactions with α2,6-linked sialic acid LSTc. Viral isolates from individuals PML often contain mutations...

JC virus (JCV) is a human polyomavirus and the causative agent of fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). JCV infection host cells dependent on interactions with cell surface asparagine (N)-linked sialic acids serotonin 5-hydroxytryptamine(2A) receptor (5-HT(2A)R). The 5-HT(2A)R contains five potential N-linked glycosylation sites extracellular N terminus. Glycosylation other receptors essential for expression, ligand binding, function. Also, cellular...

ABSTRACT JC polyomavirus (JCPyV) establishes a lifelong persistence in roughly half the human population worldwide. The cells and tissues that harbor persistent virus vivo are not known, but renal tubules other urogenital epithelial likely candidates as is shed urine of healthy individuals. In an immunosuppressed host, JCPyV can become reactivated cause progressive multifocal leukoencephalopathy (PML), fatal demyelinating disease central nervous system. Recent observations indicate may...

The human polyomavirus JC virus (JCV) infects 70% of the population worldwide. In immunosuppressed patients, JCV infection can lead to progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease central nervous system (CNS). majority PML cases occur in setting immunodeficiency (HIV) infection, and it has been suggested that link between HIV development is part related production numerous cytokines CNS during infection. To examine expression inflammatory we tested an...

JC polyomavirus (JCPyV) is a ubiquitous human pathogen that causes progressive multifocal leukoencephalopathy (PML). The entry receptors for JCPyV belong to the 5-hydroxytryptamine 2 receptor (5-HT2R) family, but how individual members of family function facilitate infection not known. We used proximity ligation assay (PLA) determine interacts with each 5-HT2 (5-HT2Rs) in narrow window time during entry. CRISPR-Cas9 randomly introduce stop codons gene and discovered second intracellular loop...

ABSTRACT Simian virus 40 (SV40), a polyomavirus that has served as an important model to understand many aspects of biology, induces dramatic cytoplasmic vacuolization late during productive infection monkey host cells. Although this activity led the discovery in 1960, mechanism is still not known. Pentamers major SV40 capsid protein VP1 bind ganglioside GM1, which serves cellular receptor for virus. In report, we show binding cell surface GM1 plays key role infection-induced vacuolization....

ABSTRACT Virus-encoded capsid proteins play a major role in the life cycles of all viruses. The JC virus is composed 72 pentamers protein Vp1, with one minor coat Vp2 or Vp3 center each pentamer. identical to two-thirds Vp2, and these share DNA binding domain, nuclear localization signal, Vp1-interacting domain. We demonstrate here that both myristylation site on are essential for viral cycle, including proper packaging its genome.

Abstract JC polyomavirus (JCPyV) is a small, non‐enveloped virus that persists in the kidney about half adult population. In severely immune‐compromised individuals JCPyV causes neurodegenerative disease progressive multifocal leukoencephalopathy (PML) brain. has been shown to infect cells by both direct and indirect mechanisms, latter involving extracellular vesicle (EV) mediated infection. While mechanisms of infection are well studied EV poorly understood. Using combination chemical...

JC virus (JCV) is a common human polyomavirus that infects over 70% of the population worldwide. JCV has restricted cell tropism caused partly by initial interaction between and sialic acid-containing host receptors. To identify molecular interactions its cellular receptor, we used combined approach site-directed mutagenesis homology-based modeling. A model major viral capsid protein VP1 based on sequence alignment with other closely related polyomaviruses allowed us to target specific amino...

Simian virus-40 (SV40) is a DNA tumour virus that was introduced into the human population with contaminated poliovirus vaccine, and its role in mesothelioma widely debated. PCR based testing has been called question, as false positives can be because of cross-reactivity related viruses, or to laboratory contamination. The Institute Medicine recommended development more sensitive specific tests resolve this controversy. We have characterized highly RT–PCR assays are for SV40-encoded...

Trichodysplasia spinulosa-associated Polyomavirus (TSPyV) was isolated from a patient suffering trichodysplasia spinulosa, skin disease that can appear in severely immunocompromised patients. While TSPyV is one of the five members polyomavirus family are directly linked to human disease, details about molecular recognition events, viral entry pathway, and intracellular trafficking events during infection remain unknown. Here we have used structure-function approach shed light on first steps...

JC polyomavirus (JCPyV) infection of immunocompromised individuals results in the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). The viral capsid JCPyV is composed primarily major protein virus 1 (VP1), and pentameric arrangement VP1 monomers formation a pore at 5-fold axis symmetry. While presence this conserved among polyomaviruses, its functional role or assembly unknown. Here, we investigate by generating panel mutant viruses containing amino acid...