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...

The human polyomavirus JC virus (JCV) infects myelin-producing cells in the central nervous system, resulting fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). JCV-induced PML occurs most frequently immunosuppressed individuals, with highest incidence immunodeficiency type 1-infected patients, ranging between 4 and 6% of all AIDS cases. Although JCV targets a highly specialized cell infection is widespread, more than 80% population worldwide demonstrating serum...

ABSTRACT The human polyomavirus JC virus (JCV) is the etiologic agent of a fatal central nervous system (CNS) demyelinating disease known as progressive multifocal leukoencephalopathy (PML). PML occurs predominantly in immunosuppressed patients and has increased dramatically result AIDS pandemic. major target cell JCV infection lytic replication CNS oligodendrocyte. mechanisms by which initiates establishes these glial cells are not understood. initial interaction between involves binding to...

To the Editor: Polyomavirus type BK nephropathy is an aggressively destructive disease occurring in up to 8 percent of patients with renal allografts,1,2 rates graft loss within one year 30 65 percent.3,4 There no therapy proven efficacy. Leflunomide (Arava), approved for treatment rheumatoid arthritis, immunosuppressive drug, yet its active metabolite, A77 1726, has substantial antiviral activity vitro and animals.5 From July 2001 April 2004, we used leflunomide as initial 17 biopsy-proven...

Background. Polyoma BK virus produces an aggressively destructive nephropathy in approximately 3% to 8% of renal allografts, is associated with graft loss within one year 35% 67% those infected and there no therapy proven efficacy. Leflunomide immune suppressive drug anti viral activity vitro animals. Methods. We treated twenty-six patients biopsy NK (BKN) either leflunomide alone (n=17) or plus a course cidofovir (n=9) followed them for six forty months. was dosed targeted blood level...

MicroRNAs (miRNAs) are potent RNA regulators of gene expression. Some viruses encode miRNAs, most unknown function. The majority viral miRNAs not conserved, and whether any have conserved functions remains unclear. Here, we report that two human polyomaviruses associated with serious disease in immunocompromised individuals, JC virus BK virus, the same function as monkey polyomavirus simian 40 miRNAs. These expressed late during infection to autoregulate early We show generated from both...

Despite major advances in our understanding of many aspects human papillomavirus (HPV) biology, HPV entry is poorly understood. To identify cellular genes required for entry, we conducted a genome-wide screen siRNAs that inhibited infection HeLa cells by HPV16 pseudovirus. Many retrograde transport factors were efficient infection, including multiple subunits the retromer, which initiates from endosome to trans-Golgi network (TGN). The retromer has not been previously implicated virus entry....

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...

Human immunodeficiency virus type 1 (HIV-1) infection of the developing central nervous system results in a dementing process children, termed HIV-1-associated encephalopathy. Infection astroglial elements pediatric has been demonstrated and suggests that direct some astrocytes may contribute to neurologic deficit. In this model, HIV-1 establishes persistent state astrocytes, which can be reactivated by cytokines tumor necrosis factor alpha (TNF-alpha) interleukin beta (IL-1 beta). To better...

The human JC polyomavirus (JCV) is the etiologic agent of fatal central nervous system (CNS) demyelinating disease progressive multifocal leukoencephalopathy (PML). PML typically occurs in immunosuppressed patients and direct result JCV infection oligodendrocytes. initial event cells by attachment virus to receptors present on surface a susceptible cell. Our laboratory has been studying this critical life cycle JCV, we have found that binds limited number cell glial are not shared related...

Polyomavirus-associated nephropathy occurs in approximately 5% of renal transplant recipients and results loss graft function 50 to 70% these patients. The disease is caused by reactivation the common human polyomavirus BK (BKV) transplanted kidney. early events productive BKV infection are unknown. In this report, we focus on elucidating mechanisms internalization its target cell. Our data reveal that entry into permissive Vero cells slow, independent clathrin-coated-pit assembly, dependent...

ABSTRACT Simian virus 40 (SV40) is a nonenveloped DNA that traffics through the endoplasmic reticulum (ER) en route to nucleus, but mechanisms of capsid disassembly and ER exit are poorly understood. We conducted an unbiased RNA interference screen identify cellular genes required for SV40 infection. infection was specifically inhibited by up 50-fold knockdown four different DNAJ molecular cochaperones or inhibition BiP, Hsp70 partner DNAJB11. These proteins were not initiation disassembly,...

Viruses within a family often vary in their cellular tropism and pathogenicity. In many cases, these variations are due to viruses switching specificity from one cell surface receptor another. The structural requirements that underlie such not well understood especially for carbohydrate-binding viruses, as methods capable of structure-specificity studies only relatively recently being developed carbohydrates. We have characterized the specificity, structure infectivity human polyomavirus...

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...

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...

The class I molecules encoded by the major histocompatibility complex (MHC) present endogenously synthesized antigenic peptide fragments to cytotoxic T lymphocytes. We show here that these proteins are an essential component of cell surface receptor for simian virus 40 (SV40). First, SV40 binding cells can be blocked two monoclonal antibodies against human lymphocyte antigen (HLA) but not specific other proteins. Second, does bind different lymphoblastoid lines which do express MHC because...