Orderly Steps in Progression of JC Virus to Virulence in the Brain

Johnson, Edward M.; Wortman, Margaret J.; Lundberg, Patric; Daniel, Dianne C.

doi:10.4172/2168-975x.s2-003

Cited by 3 publications

(2 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the vast majority of adults are seropositive for JCV, the virus, at low infection levels in kidney epithelial tissue and bone marrow, rarely causes any symptoms. Under certain immunosuppressive conditions, however, JCV undergoes genetic changes in its non-coding replication/transcription control region and gains the ability to infect oligodendrocytes in the brain (Johnson et al, 2015). In this case Pura acts by altering both gene expression (Chen et al, 1995; Krachmarov et al, 1996; Gallia et al, 1998; White et al, 2009; Sariyer et al, 2016) and replication of JCV (Chen et al, 1995; Krachmarov et al, 1996; Wortman et al, 2000; Daniel et al, 2001; Reiss and Khalili, 2003; Daniel et al, 2004).…”

Section: Role Of Pura In Brain Development Neuronal Function and mentioning

confidence: 99%

PURA , the gene encoding Pur-alpha, member of an ancient nucleic acid-binding protein family with mammalian neurological functions

Daniel

Johnson

2018

Gene

View full text Add to dashboard Cite

The PURA gene encodes Pur-alpha, a 322 amino acid protein with repeated nucleic acid binding domains that are highly conserved from bacteria through humans. PUR genes with a single copy of this domain have been detected so far in spirochetes and bacteroides. Lower eukaryotes possess one copy of the PUR gene, whereas chordates possess 1 to 4 PUR family members. Human PUR genes encode Pur-alpha (Pura), Pur-beta (Purb) and two forms of Pur-gamma (Purg). Pur-alpha is a protein that binds specific DNA and RNA sequence elements. Human PURA, located at chromosome band 5q31, is under complex control of three promoters. The entire protein coding sequence of PURA is contiguous within a single exon. Several studies have found that overexpression or microinjection of Pura inhibits anchorage-independent growth of oncogenically transformed cells and blocks proliferation at either G1-S or G2-M checkpoints. Effects on the cell cycle may be mediated by interaction of Pura with cellular proteins including Cyclin/Cdk complexes and the Rb tumor suppressor protein. PURA knockout mice die shortly after birth with effects on brain and hematopoietic development. In humans environmentally induced heterozygous deletions of PURA have been implicated in forms of myelodysplastic syndrome and progression to acute myelogenous leukemia. Pura plays a role in AIDS through association with the HIV-1 protein, Tat. In the brain Tat and Pura association in glial cells activates transcription and replication of JC polyomavirus, the agent causing the demyelination disease, progressive multifocal leukoencephalopathy. Tat and Pura also act to stimulate replication of the HIV-1 RNA genome. In neurons Pura accompanies mRNA transcripts to sites of translation in dendrites. Microdeletions in the PURA locus have been implicated in several neurological disorders. De novo PURA mutations have been related to a spectrum of phenotypes indicating a potential PURA syndrome. The nucleic acid, G-rich Pura binding element is amplified as expanded polynucleotide repeats in several brain diseases including fragile X syndrome and a familial form of amyotrophic lateral sclerosis/fronto-temporal dementia. Throughout evolution the Pura protein plays a critical role in survival, based on conservation of its nucleic acid binding properties. These Pura properties have been adapted in higher organisms to the as yet unfathomable development of the human brain.

show abstract

Section: Role Of Pura In Brain Development Neuronal Function and mentioning

confidence: 99%

PURA , the gene encoding Pur-alpha, member of an ancient nucleic acid-binding protein family with mammalian neurological functions

Daniel

Johnson

2018

Gene

View full text Add to dashboard Cite

show abstract

“…Previous results, however, have led up to this finding [2], and the replication properties of these two viruses provide special circumstances for their interaction. Recombination between human viruses has been frequently documented, generally involving two viruses of the same class or two distinct but closely related viruses, such as HIV-1 and HIV-2 [3].…”

Section: Introductionmentioning

confidence: 88%

Significance of Interviral Recombination as Novel Mechanism for Extending Viral Disease Repertoire

Johnson

Daniel

2016

Brain Disord Ther

Self Cite

View full text Add to dashboard Cite

The recent observation of interviral recombination between members of two distinct classes of DNA viruses has opened the gates to a new field of human disease development. In all cases studied thus far interviral recombination is a rare event that requires special circumstances for intracellular interaction of participating viral genomes. The rarity and special requirements do not detract from the potential clinical significance of resulting recombinants, as exemplified by recombination between JC viral and Epstein-Barr viral genomes. This significance depends largely upon the mechanisms of recombination that would generate specific forms of recombinant viral genomes. At this time little is known regarding mechanisms of interviral recombination. DNA break-induced replication seems presently to be a highly plausible means of initiating formation of different, potentially active recombination products. Generalizing interviral recombination to a variety of viruses will open a fertile field for discovery as multiple diseases of mysterious etiology are investigated.

show abstract

Effect of deep brain stimulation on sexual dysfunction among patients who had Parkinson’s disease: a systematic review and meta-analysis

Bahadori,

Zafari,

Fathollahi

et al. 2024

Neurological Research

View full text Add to dashboard Cite

show abstract

Orderly Steps in Progression of JC Virus to Virulence in the Brain

Cited by 3 publications

References 12 publications

PURA , the gene encoding Pur-alpha, member of an ancient nucleic acid-binding protein family with mammalian neurological functions

PURA , the gene encoding Pur-alpha, member of an ancient nucleic acid-binding protein family with mammalian neurological functions

Significance of Interviral Recombination as Novel Mechanism for Extending Viral Disease Repertoire

Effect of deep brain stimulation on sexual dysfunction among patients who had Parkinson’s disease: a systematic review and meta-analysis

Contact Info

Product

Resources

About