Novel Replication-Competent Circular DNA Molecules from Healthy Cattle Serum and Milk and Multiple Sclerosis-Affected Human Brain Tissue

Whitley, Corinna; Gunst, Karin; Müller, Hermann; Funk, Mathis; Hausen, Harald zur; Villiers, Ethel‐Michele de

doi:10.1128/genomea.00849-14

Cited by 39 publications

(62 citation statements)

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“…The origin of the gemycircularvirus DNA found here in CSF and recently described in human and bovine plasma (Whitley et al, 2014) also remains uncertain. To date the only cellular host identified is for the prototype of this group, SsHADV-1, the first DNA virus shown to replicate in fungi (Yu et al, 2010).…”

Section: Discussionmentioning

confidence: 77%

Small circular single stranded DNA viral genomes in unexplained cases of human encephalitis, diarrhea, and in untreated sewage

et al. 2015

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Viruses with small circular rep-encoding ssDNA (CRESS-DNA) genomes can infect a wide range of eukaryotic organisms ranging from mammals to fungi. The genomes of two novel CRESS-DNA viruses, a cyclovirus (CyCV-SL) and gemycircularvirus (GemyCVSL) were detected by deep sequencing of the cerebrospinal fluids of Sri Lankan patients with unexplained encephalitis. One and three out of 201 CSF samples (1.5%) from unexplained encephalitis patients tested by PCR were CyCV-SL and GemyCV-SL DNA positive respectively. Nucleotide similarity searches of pre-existing datasets revealed related genomes in feces from unexplained cases of diarrhea from Nicaragua and Brazil and in untreated sewage from Nepal. Whether the tropism of the cycloviruses and gemycircularviruses reported here include humans or their detection reflects production from other cellular sources in or on the human body remains to be determined.

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Section: Discussionmentioning

confidence: 77%

Small circular single stranded DNA viral genomes in unexplained cases of human encephalitis, diarrhea, and in untreated sewage

et al. 2015

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“…It remains to be seen if their transcriptional activity, or antibody detected Rep A or other ORF proteins give them different attributes. SPHINX DNAs were not detectable in our reagents in numerous tests, indicating they were not lab contaminants, and the 1.76 element was identified in two human Multiple Sclerosis brains and sera in Germany [Whitley et al, ]. This further independently links them to progressive brain pathology.…”

Section: Discussionmentioning

confidence: 81%

“…However, antibodies to a cognate viral replication (RepA) protein (gift of D. Siddavattam, [Longkumer et al, ]) confirm they are transcriptionally active viral elements in both our infected and uninfected mammalian cells (unpublished observations). The identical 1.76 kb SPHINX sequence has also been independently confirmed in human material, including two Multiple Sclerosis brains [Whitley et al, ]. Thus PCR for mtDNA and SPHINX DNAs here provided sensitive internal viral controls for evaluating the effectiveness of nuclease digestions in parallel with the destruction of infectivity.…”

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confidence: 61%

CJD and Scrapie Require Agent‐Associated Nucleic Acids for Infection

Botsios¹,

Manuelidis²

2016

J of Cellular Biochemistry

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Unlike Alzheimer's and most other neurodegenerative diseases, Transmissible Spongiform Encephalopathies (TSEs) are all caused by actively replicating infectious particles of viral size and density. Different strain-specific TSE agents cause CJD, kuru, scrapie and BSE, and all behave as latent viruses that evade adaptive immune responses and can persist for years in lymphoreticular tissues. A foreign viral structure with a nucleic acid genome best explains these TSE strains and their endemic and epidemic spread in susceptible species. Nevertheless, it is widely believed that host prion protein (PrP), without any genetic material, encodes all these strains. We developed rapid infectivity assays that allowed us to reproducibly isolate infectious particles where >85% of the starting titer separated from the majority of host components, including PrP. Remarkably, digestion of all forms of PrP did not reduce brain particle titers. To ask if TSE agents, as other viruses, require nucleic acids, we exposed high titer FU-CJD and 22L scrapie particles to potent nucleases. Both agent-strains were propagated in GT1 neuronal cells to avoid interference by complex degenerative brain changes that can impede nuclease digestions. After exposure to nucleases that are active in sarkosyl, infectivity of both agents was reproducibly reduced by ≥99%. No gold-stained host proteins or any form of PrP were visibly altered by these nucleases. In contrast, co-purifying protected mitochondrial DNA and circular SPHINX DNAs were destroyed. These findings demonstrate that TSE agents require protected genetic material to infect their hosts, and should reopen investigation of essential agent nucleic acids. J. Cell. Biochem. 117: 1947-1958, 2016. © 2016 Wiley Periodicals, Inc.

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“…CMI3.168 was isolated from milk, yogurt, and curd cheese, CMI4.158 from milk, and healthy cattle blood isolate (HCBI) 6.252 from milk and yogurt (3). …”

Section: Genome Announcementmentioning

confidence: 99%

Isolation of Two Virus-Like Circular DNAs from Commercially Available Milk Samples

et al. 2017

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Novel Replication-Competent Circular DNA Molecules from Healthy Cattle Serum and Milk and Multiple Sclerosis-Affected Human Brain Tissue

Cited by 39 publications

References 5 publications

Small circular single stranded DNA viral genomes in unexplained cases of human encephalitis, diarrhea, and in untreated sewage

Small circular single stranded DNA viral genomes in unexplained cases of human encephalitis, diarrhea, and in untreated sewage

CJD and Scrapie Require Agent‐Associated Nucleic Acids for Infection

Isolation of Two Virus-Like Circular DNAs from Commercially Available Milk Samples

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