Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human polyomavirus JC (JCV) typically infects glial cells and is the aetiological agent of progressive multifocal leukoencephalopathy (PML), which occurs in immunosuppressed individuals. The full-length sequence of a granule cell neuron-tropic JCV variant, JCV(GCN1), associated with lytic infection of granule cell neurons and cerebellar atrophy in a human immunodeficiency virus-infected patient with PML was determined and compared with the sequence of the JCV isolate from the classic PML lesions present in the hemispheric white matter of the same individual (JCV(HWM)). A unique deletion was found in the C terminus of the VP1 gene of JCV(GCN1), which encodes the major capsid protein, resulting in a frame shift and a total change of the C-terminal amino acid sequence of this protein. This deletion was not present in JCV(HWM), suggesting that this mutation may be instrumental in facilitating entry or replication of JCV into granule cell neurons.
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PMID:A granule cell neuron-associated JC virus variant has a unique deletion in the VP1 gene. 1689 91

The polyomavirus JC (JCV) infects glial cells and causes progressive multifocal leukoencephalopathy (PML). We described a novel JCV-variant with a 10 bp deletion in the C terminus of the VP1 capsid protein, JCV(GCN1). This mutant was associated with lytic infection of cerebellar granule cell neurons and cerebellar atrophy in an human immunodeficiency virus/PML patient. This condition, also observed independently from PML, was named JCV granule cell neuronopathy (JCV GCN). We characterized JCV mutations in cerebrospinal fluid (CSF) of four other JCV GCN patients, and reviewed the literature on 10 reported cases. The strain from one patient harboured the identical GCN1-deletion, while the other patients had novel mutations in the same area, named JCV(GCN2-4), causing variable changes in VP1 structure. One patient also had wild-type JCV in the CSF. To study the mechanisms leading to JCV GCN, we compared viral replication kinetics from JCV(GCN1) with the prototype JCV(Mad1), the PML isolate JCV(HWM) and the prototype JCV(Mad1D) engineered with the GCN1-deletion. While all strains replicated at low levels in the medulloblastoma cell line DAOY from a cerebellar neuronal tumour, JCV(Mad1) replicated better in astroglial SVG cells than JCV(Mad1D) or JCV(GCN1) and all strains replicated at higher levels in COS-7 kidney cells, suggesting that the GCN1-deletion confers a disadvantage for viral growth in central nervous system white matter. The GCN1-deletion remained stable after 100 days in culture and VP1 protein was produced in all cell lines, indicating that JCV(GCN1) is replication-competent in vitro. These data highlight an important and previously overlooked aspect of JCV-pathogenesis. Detection of GCN-type JCV strains in CSF may help clinicians diagnose JCV GCN.
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PMID:JC virus granule cell neuronopathy is associated with VP1 C terminus mutants. 2194 Apr 15