PMID- 26874214
OWN - NLM
STAT- MEDLINE
DCOM- 20160719
LR  - 20220311
IS  - 1531-8249 (Electronic)
IS  - 0364-5134 (Linking)
VI  - 79
IP  - 3
DP  - 2016 Mar
TI  - Mechanisms of immune escape in central nervous system infection with neurotropic 
      JC virus variant.
PG  - 404-18
LID - 10.1002/ana.24574 [doi]
AB  - OBJECTIVE: Symptomatic infections of the central nervous system (CNS) with JC 
      polyomavirus (JCV) usually occur as a result of immunocompromise and manifest as 
      progressive multifocal leukoencephalopathy (PML) or granule cell neuronopathy 
      (GCN). After immune reconstitution, some of these cases may show long-term 
      persistence of JCV and delayed clinical improvement despite inflammation. 
      METHODS: We followed 4 patients with multiple sclerosis, who developed 
      natalizumab-associated PML or GCN with regard to JC viral load and JCV-specific 
      T-cell responses in the CNS. All of them experienced immune reconstitution 
      inflammatory syndrome (IRIS), but in 2 cases JCV persisted > 21 months after IRIS 
      accompanied by delayed clinical improvement. RESULTS: Persistence of JCV was 
      associated with a lack of JCV VP1-specific T-cell responses during immune 
      reconstitution in 1 of the patients. Detailed analysis of the brain infiltrate in 
      another patient with neuronal persistence of JCV revealed strong infiltration of 
      CD8(+) T cells and clonal expansion of activated CD8(+) effector T cells with a 
      CD4(dim) CD8(+) phenotype, both exhibiting exquisite specificity for conserved 
      epitopes of JCV large T antigen. However, clearance of JCV was not efficient, 
      because mutations in the major capsid protein VP1 caused reduced CD4(+) T-cell 
      responses against the identified JCV variant and subsequently resulted in a 
      decline of CD8(+) T-cell responses after IRIS. INTERPRETATION: Our findings 
      suggest that efficient CD4(+) T-cell recognition of neurotropic JCV variants is 
      crucial to support CD8(+) T cells in combating JCV infection of the CNS.
CI  - (c) 2016 American Neurological Association.
FAU - Jelcic, Ivan
AU  - Jelcic I
AD  - Neuroimmunology and Multiple Sclerosis Research Section, Department of Neurology 
      University Hospital Zurich, Zurich, Switzerland.
FAU - Jelcic, Ilijas
AU  - Jelcic I
AD  - Neuroimmunology and Multiple Sclerosis Research Section, Department of Neurology 
      University Hospital Zurich, Zurich, Switzerland.
FAU - Kempf, Christian
AU  - Kempf C
AD  - Neuroimmunology and Multiple Sclerosis Research Section, Department of Neurology 
      University Hospital Zurich, Zurich, Switzerland.
FAU - Largey, Fabienne
AU  - Largey F
AD  - Neuroimmunology and Multiple Sclerosis Research Section, Department of Neurology 
      University Hospital Zurich, Zurich, Switzerland.
FAU - Planas, Raquel
AU  - Planas R
AD  - Neuroimmunology and Multiple Sclerosis Research Section, Department of Neurology 
      University Hospital Zurich, Zurich, Switzerland.
FAU - Schippling, Sven
AU  - Schippling S
AD  - Neuroimmunology and Multiple Sclerosis Research Section, Department of Neurology 
      University Hospital Zurich, Zurich, Switzerland.
FAU - Budka, Herbert
AU  - Budka H
AD  - Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.
FAU - Sospedra, Mireia
AU  - Sospedra M
AD  - Neuroimmunology and Multiple Sclerosis Research Section, Department of Neurology 
      University Hospital Zurich, Zurich, Switzerland.
FAU - Martin, Roland
AU  - Martin R
AD  - Neuroimmunology and Multiple Sclerosis Research Section, Department of Neurology 
      University Hospital Zurich, Zurich, Switzerland.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160213
PL  - United States
TA  - Ann Neurol
JT  - Annals of neurology
JID - 7707449
SB  - IM
MH  - Adult
MH  - Brain/immunology/virology
MH  - Female
MH  - Humans
MH  - Immune Evasion/*immunology
MH  - Immune Reconstitution Inflammatory Syndrome/*immunology/virology
MH  - JC Virus/classification/genetics/*physiology
MH  - Leukoencephalopathy, Progressive Multifocal/*immunology/*virology
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/*immunology/virology
EDAT- 2016/02/14 06:00
MHDA- 2016/07/20 06:00
CRDT- 2016/02/14 06:00
PHST- 2015/05/10 00:00 [received]
PHST- 2015/10/20 00:00 [revised]
PHST- 2015/11/28 00:00 [accepted]
PHST- 2016/02/14 06:00 [entrez]
PHST- 2016/02/14 06:00 [pubmed]
PHST- 2016/07/20 06:00 [medline]
AID - 10.1002/ana.24574 [doi]
PST - ppublish
SO  - Ann Neurol. 2016 Mar;79(3):404-18. doi: 10.1002/ana.24574. Epub 2016 Feb 13.