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At least 433 records · Page 24Linked to original sources
PubMed1989

Regulatory sequences of SV40 variants isolated from patients with progressive multifocal leukoencephalopathy.

Variants of the simian polyomavirus SV40 have been associated in humans with a small number of cases of progressive multifocal leukoencephalopathy (PML). Genomic regulatory regions of two independent isolates, SVPML-1 and -2 [L.P. Weiner et al., N. Engl. J. Med. 286, 385 (1972)], were analyzed to determine if they had acquired any sequences that are present in the genome of the human polyomavirus JC (JCV), the primary causative agent of PML. As compared to SV40 DNA, 83% of SVPML-1 and -2 cloned DNAs contained an apparent deletion of about 30 base pairs in the restriction fragment containing the regulatory region (type alpha); 17% had a deletion of about 60 base pairs (type beta). The regulatory sequences were identical in all four clones representative of SVPML-1 and -2 type alpha grown in human and monkey cells. Thus the primary genomes of two isolates of SV40 from PML are identical in the region that is highly heterogeneous in JCV. The SVPML-alpha-DNAs have a net deletion of 30 base pairs and rearrangements within the transcriptional enhancer. The transcriptional promoter and origin of DNA replication is unaltered from that of SV40. Therefore the human neurotropism of SVPML appears to be a consequence of important rearrangements of SV40 sequences rather than acquisition of JCV-like sequences.

Base Sequence↗
PubMed2002

Detection of JC virus type 1 in peripheral lymphocytes, brain and cerebrospinal fluid from two Korean AIDS patients with progressive multifocal leukoencephalopathy.

The human polyomavirus JC virus (JCV) is the etiologic agent of the fatal demyelinating central nervous system disease progressive multifocal leukoencephalopathy (PML), which occurs in 4-7% of AIDS patients. Two Korean AIDS patients with PML were assayed for JCV, and the virus was genotyped by polymerase chain reaction, DNA sequencing and phylogenetic analysis. Using immunohistochemical analysis, we also examined the distribution of JCV antigen in the brains of the patients. The JCV genome was detected in peripheral lymphocytes, brain and cerebrospinal fluid from these Korean PML patients. Although type 2 is the most common genotype in Asia, the genotype of the JCV in these two AIDS patients was characterized as type 1, which is of European origin. We found that JCV antigen was selectively detected in oligodendrocytes and astrocytes of the brains from these patients. Compared to the prototype type 1 (Mad-1), two different nucleotides (G-->C) in the KOR-1 strain identified here were found at positions 2488 and 2490 of the major capsid protein VP1 gene. In summary, this is the first report of PML in Korean AIDS patients; it is also the first isolation of JCV type 1 in PML in East Asians.

AIDS-Related Opportunistic Infections↗
PubMed1996

Accumulation of wild-type p53 protein in progressive multifocal leukoencephalopathy: a flow of cytometry and DNA sequencing study.

p52 protein accumulation in JC virus (JCV)-infected cells of progressive multifocal leukoencephalopathy (PML) has been previously shown. Since many viral proteins are known to bind and stabilize p53, we are addressing the question of whether p53 protein accumulation in PML is the result of its sequestration by JCV and not the outcome of a p53 gene mutation which would prolong its half-life. We have investigated the status of the p53 gene in frozen autopsy brain samples from five PML patients. After isolating genomic DNA, p53 gene exons 2 through 9 were amplified and sequenced. No discrepancies were found in the DNA sequences of exons 2 through 9 and their intron/exon barriers when compared to those published for wild-type p53. On the other hand, dual (p53/DNA) flow cytometry analysis revealed p53 expression above that of the isotypic controls for each case. No aneuploid populations could be identified, however, which seems at odds with the aneuploid status normally associated with mutation-induced p53 dysfunction. These results indicate that the p53 gene harbors no mutations in PML and provide further evidence of p53 protein accumulation in this condition. Since p53 protein buildup in JCV-infected cells is not the consequence of a mutagenic interaction between JCV and the cell genome, we propose instead that p53 accumulation results from its binding and stabilization by JCV T protein.

Base Sequence↗
PubMed1999

Reduced concentrations of HIV-RNA and TNF-alpha coexist in CSF of AIDS patients with progressive multifocal leukoencephalopathy.

OBJECTIVES: To confirm reduced human immunodeficiency virus type-1 (HIV-1) burden in the CSF of patients with progressive multifocal leukoencephalopathy (PML) and to verify whether this viral load coincides with the absence of inflammatory changes in the CSF. METHODS: Paired CSF and plasma samples from 17 patients with PML, 26 with non-PML cerebral opportunistic infections, nine with HIV-1 leukoencephalopathy (HIVE), and 12 neurologically asymptomatic AIDS patients were subjected to HIV-RNA titration. Tumour necrosis factor (TNF)-alpha was also measured and the CSF albumin: serum albumin ratio (Q(Alb)) was calculated. RESULTS: The CSF HIV-1 burden of patients with PML did not differ from that of neurologically asymptomatic patients (p=0.21), but was significantly lower than CSF burden of the remaining patients (non-PML opportunistic infections, p<0.001; HIVE, p<0.001). Q(Alb) was normal for all neurologically asymptomatic patients, for 86.6% patients with PML, and 62.5% patients with HIVE (p=0.09). Q(Alb) was altered in 91.6% patients with non-PML opportunistic infections. TNF-alpha in CSF was higher in patients with non-PML opportunistic infections (p<0.001) and those with HIVE (p<0.001) than in patients with PML who consistently had TNF-alpha concentrations<10 pg/ml. CONCLUSIONS: These results, while indicating a reduced HIV replication in CSF of patients with PML which might serve as a disease marker, emphasise the increased CSF HIV-RNA concentration in patients with HIVE and patients with non-PML opportunistic infections. Low concentrations of HIV-RNA in CSF coincide with reduced TNF-alpha concentrations, possibly due to particular features of PML compared with other opportunistic infections as it develops without detectable inflammatory changes in the CSF.

Acquired Immunodeficiency Syndrome↗