Thursday, 15 March 2012

Virus-like sequences in the brains of MS'ers

Kriesel et al. Deep Sequencing for the Detection of Virus-Like Sequences in the Brains of Patients with Multiple Sclerosis: Detection of GBV-C in Human Brain. PLoS One. 2012;7(3):e31886. Epub 2012 Mar 8. 

GBV-C or hepatitis G is a flavivirus that is found in the serum of 1-2% of blood donors. It was originally associated with hepatitis, but is now believed to be a relatively non-pathogenic lymphotropic virus (infects lymphocytes). 

50 frozen specimens from the brains of deceased persons affected by MS were obtained along with 15 normal control brain specimens. RNA (type of nucleic acid that is related to DNA) was extracted and ribosomal RNAs were depleted before sequencing on the Illumina GAII. These 36 bp reads were compared with a non-redundant database derived from the 600,000+ viral sequences in GenBank organized into 4080 taxa. An individual read successfully aligned to the viral database was considered to be a "hit". Normalized MS specimen hit rates for each viral taxon (families of viruses) were compared to the distribution of hits in the normal controls. 

17 MS and 11 control brain extracts were sequenced, yielding 4-10 million sequences ("reads") each. Over-representation of sequence from at least one of 12 viral taxa was observed in 7 of the 17 MS samples. Sequences resembling other viruses previously implicated in the pathogenesis of MS were not significantly enriched in any of the diseased brain specimens. Sequences from GB virus C (GBV-C), a flavivirus not previously isolated from brain, were enriched in one of the MS samples. GBV-C in this brain specimen was confirmed by specific amplification in this single MS brain specimen, but not in the 30 other MS brain samples available. The entire 9.4 kb sequence of this GBV-C isolate is reported here. 
This study shows the feasibility of deep sequencing (a new technique) for the detection of occult viral infections in the brains of deceased persons with MS. The first isolation of GBV-C from human brain is reported here.

"This is an interesting finding and shows that a new technique of RNA/DNA sequencing can be applied to the brains of MS'ers. We should join the party."

"This work will need to be repeated. The most important experiment will be to look at the cortex or gray matter lesions and to try and look at very early lesions; the Barnet-Prineas lesion without much inflammation but massive apoptosis of oligodendrocytes."

"A cool study!"

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