Capsid protein VP1 deletions in JC virus from two AIDS patients with progressive multifocal leukoencephalopathy

1995 ◽  
Vol 1 (2) ◽  
pp. 189-194 ◽  
Author(s):  
Gerald L Stoner ◽  
Caroline F Ryschkewitsch
Keyword(s):  
Progressive Multifocal Leukoencephalopathy ◽  
Capsid Protein ◽  
Jc Virus ◽  
Aids Patients ◽  
Capsid Protein Vp1

scholarly journals Treating Progressive Multifocal Leukoencephalopathy With Interleukin 7 and Vaccination With JC Virus Capsid Protein VP1

2014 ◽  
Vol 59 (11) ◽  
pp. 1588-1592 ◽  
Author(s):  
Mireia Sospedra ◽  
Sven Schippling ◽  
Sara Yousef ◽  
Ilijas Jelcic ◽  
Silvia Bofill-Mas ◽  
...  
Keyword(s):  
Progressive Multifocal Leukoencephalopathy ◽  
Capsid Protein ◽  
Jc Virus ◽  
Virus Capsid ◽  
Interleukin 7 ◽  
Capsid Protein Vp1 ◽  
Virus Capsid Protein

scholarly journals Antibody escape by polyomavirus capsid mutation facilitates neurovirulence

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Matthew D Lauver ◽  
Daniel J Goetschius ◽  
Colleen S Netherby-Winslow ◽  
Katelyn N Ayers ◽  
Ge Jin ◽  
...  
Keyword(s):  
Progressive Multifocal Leukoencephalopathy ◽  
Capsid Protein ◽  
Neutralizing Antibody ◽  
Viral Capsid ◽  
Cell Tropism ◽  
Capsid Protein Vp1 ◽  
Particle Refinement ◽  
Immunomodulatory Therapies ◽  
Major Viral Capsid Protein

JCPyV polyomavirus, a member of the human virome, causes progressive multifocal leukoencephalopathy (PML), an oft-fatal demyelinating brain disease in individuals receiving immunomodulatory therapies. Mutations in the major viral capsid protein, VP1, are common in JCPyV from PML patients (JCPyV-PML) but whether they confer neurovirulence or escape from virus-neutralizing antibody (nAb) in vivo is unknown. A mouse polyomavirus (MuPyV) with a sequence-equivalent JCPyV-PML VP1 mutation replicated poorly in the kidney, a major reservoir for JCPyV persistence, but retained the CNS infectivity, cell tropism, and neuropathology of the parental virus. This mutation rendered MuPyV resistant to a monoclonal Ab (mAb), whose specificity overlapped the endogenous anti-VP1 response. Using cryo-EM and a custom sub-particle refinement approach, we resolved an MuPyV:Fab complex map to 3.2 Å resolution. The structure revealed the mechanism of mAb evasion. Our findings demonstrate convergence between nAb evasion and CNS neurovirulence in vivo by a frequent JCPyV-PML VP1 mutation.

scholarly journals Progressive multifocal leukoencephalopathy in human immunodeficiency virus type 1-infected patients: absence of correlation between JC virus neurovirulence and polymorphisms in the transcriptional control region and the major capsid protein loci

2001 ◽  
Vol 82 (4) ◽  
pp. 899-907 ◽  
Author(s):  
Monica Sala ◽  
Jean-Pierre Vartanian ◽  
Pascale Kousignian ◽  
Jean-François Delfraissy ◽  
Yassine Taoufik ◽  
...  
Keyword(s):  
Progressive Multifocal Leukoencephalopathy ◽  
Capsid Protein ◽  
Control Region ◽  
Transcriptional Control ◽  
Major Capsid Protein ◽  
Demyelinating Disease ◽  
Jc Virus ◽  
Capsid Protein Gene ◽  
Transcriptional Control Region ◽  
Genomic Marker

Progressive multifocal leukoencephalopathy (PML) is a rapidly fatal demyelinating disease of the central nervous system related to JC polyomavirus (JCV) replication in oligodendrocytes. PML usually occurs in immunocompromised individuals, especially in the setting of AIDS. Administration of highly active anti-retroviral therapy (HAART) may improve survival prognosis in some, but not all, patients with AIDS-related PML. This observation might be explained by the outgrowth of some JCV variants of increased fitness. To evaluate this hypothesis, two subgroups of five patients with AIDS-related PML, started on HAART after PML diagnosis, were analysed. The non-responder (NR) patients died rapidly despite HAART, while responders (R) had a positive outcome and were still alive. JCV DNA was extracted from cerebrospinal fluid biopsies and two regions of the genome were analysed, the transcriptional control region (TCR) and the major capsid protein gene (VP1). Both regions show different degrees of polymorphism and are recognized as evolving independently. Sequence analysis demonstrated that (i) extensive TCR rearrangements were present in both subgroups of patients, (ii) VP1 sequence polymorphisms could be identified in the BC loop, suggesting the absence of immune selection, and (iii) no genomic marker for JCV specific neurovirulence could be identified in the TCR and VP1 loci.

Production of the antigen and the antibody of the JC virus major capsid protein VP1

1996 ◽  
Vol 59 (1-2) ◽  
pp. 177-187 ◽  
Author(s):  
Deching Chang ◽  
Zeu-Maun Liou ◽  
Wei-Chih Ou ◽  
Kai-Ziu Wang ◽  
Meilin Wang ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Major Capsid Protein ◽  
Jc Virus ◽  
Capsid Protein Vp1

Human anti-JC virus serum reacts with native but not denatured JC virus major capsid protein VP1

1999 ◽  
Vol 78 (1-2) ◽  
pp. 171-176 ◽  
Author(s):  
Meilin Wang ◽  
Tsair-Yuh Tzeng ◽  
Chiung-Yau Fung ◽  
Wei-Chih Ou ◽  
Rong-Tai Tsai ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Major Capsid Protein ◽  
Jc Virus ◽  
Capsid Protein Vp1

scholarly journals Antibody Escape by Polyomavirus Capsid Mutation Facilitates Neurovirulence

2020 ◽  
Author(s):  
Matthew D. Lauver ◽  
Daniel J. Goetschius ◽  
Colleen S. Netherby-Winslow ◽  
Katelyn N. Ayers ◽  
Ge Jin ◽  
...  
Keyword(s):  
Progressive Multifocal Leukoencephalopathy ◽  
Capsid Protein ◽  
Neutralizing Antibody ◽  
Parental Virus ◽  
Viral Capsid ◽  
Cell Tropism ◽  
Capsid Protein Vp1 ◽  
Immunomodulatory Therapies ◽  
Major Viral Capsid Protein

SUMMARYJCPyV polyomavirus, a member of the human virome, causes Progressive Multifocal Leukoencephalopathy (PML), an oft-fatal demyelinating brain disease in individuals receiving immunomodulatory therapies. Mutations in the major viral capsid protein, VP1, are common in JCPyV from PML patients (JCPyV-PML) but whether they confer neurovirulence or escape from virus-neutralizing antibody (nAb) in vivo is unknown. A mouse polyomavirus (MuPyV) with a sequence-equivalent JCPyV-PML VP1 mutation replicated poorly in the kidney, a major reservoir for JCPyV persistence, but retained the CNS infectivity, cell tropism, and neuropathology of the parental virus. This mutation rendered MuPyV resistant to a monoclonal Ab (mAb), whose specificity overlapped the endogenous anti-VP1 response. Using cryo EM and a custom subvolume refinement approach, we resolved an MuPyV:Fab complex map to 3.1 Å resolution. The structure revealed the mechanism of mAb evasion. Our findings demonstrate convergence between nAb evasion and CNS neurovirulence in vivo by a frequent JCPyV-PML VP1 mutation.

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