The Human Bone Marrow Is Host to the DNAs of Several Viruses

Toppinen, Mari; Sajantila, Antti; Pratas, Diogo; Hedman, Klaus; Perdomo, Maria F.

doi:10.3389/fcimb.2021.657245

Cited by 13 publications

(14 citation statements)

References 56 publications

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“…The authors found that the MSCs derived from healthy donors contained viral DNA of parvovirus B19. Viral DNA has also been found in human bone marrow ( 43 ). The most common were B19V and torque teno virus (TTV): 62.9%, Epstein-Barr virus (EBV): 14.8%, Merkel cell polyomavirus (MCPyV): 11.1%, and human herpesvirus 7 (HHV-7): 7.4%.…”

Section: Viral and Mycoplasma Containment In Mscsmentioning

confidence: 99%

Adverse events, side effects and complications in mesenchymal stromal cell-based therapies

Baranovskii¹,

Klabukov²,

Arguchinskaya³

et al. 2022

Stem Cell Investig

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Numerous clinical studies have shown a wide clinical potential of mesenchymal stromal cells (MSCs) application. However, recent experience has accumulated numerous reports of adverse events and side effects associated with MSCs therapy. Furthermore, the strategies and methods of MSCs therapy did not change significantly in recent decades despite the clinical impact and awareness of potential complications.An extended understanding of limitations could lead to a wider clinical implementation of safe cell therapies and avoid harmful approaches. Therefore, our objective was to summarize the possible negative effects observed during MSCs-based therapies. We were also aimed to discuss the risks caused by weaknesses in cell processing, including isolation, culturing, and storage. Cell processing and cell culture could dramatically influence cell population profile, change protein expression and cell differentiation paving the way for future negative effects. Long-term cell culture led to accumulation of chromosomal abnormalities.Overdosed antibiotics in culture media enhanced the risk of mycoplasma contamination. Clinical trials reported thromboembolism and fibrosis as the most common adverse events of MSCs therapy. Their delayed manifestation generally depends on the patient's individual phenotype and requires specific awareness during the clinical trials with obligatory inclusion in the patient' informed consents. Finally we prepared the safety checklist, recommended for clinical specialists before administration or planning of MSCs therapy.

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Section: Viral and Mycoplasma Containment In Mscsmentioning

confidence: 99%

Adverse events, side effects and complications in mesenchymal stromal cell-based therapies

Baranovskii¹,

Klabukov²,

Arguchinskaya³

et al. 2022

Stem Cell Investig

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show abstract

“…HBV DNA can be found in the liver beyond serological resolution of chronic infection (termed occult HBV infection, OBI)[87,88], however, HBV persistence in other organs during OBI has been limitedly described. Evidence of extra-hepatic HBV DNA also exists in ancient and modern bones [36,89] and in bone marrow [43]. Together these ndings call for further assessment of the infectivity of all organs from chronic HBV carriers in transplantation medicine [88,90].…”

Section: Discussionmentioning

confidence: 99%

“…The baits were 100 nucleotides long, designed with 2X tiling, and targeted the full-length sequences of 38 human DNA viruses (parvovirus B19; torque teno virus; nine herpesviruses; polyomaviruses 1-13; hepatitis B virus; papillomavirus types 2, 6, 11, 16, 18, 21, 45; bocaviruses 1-4; cutavirus; simian virus 40; and variola viruses minor and major), as described [36,43].…”

Section: Viral Enrichment and Deep Sequencingmentioning

confidence: 99%

Unmasking the Tissue-Resident Eukaryotic DNA Virome in Humans

Pyöriä

Pratas

Toppinen

et al. 2022

Preprint

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Background Little is known on the landscape of viruses that have taken residence within our cells, nor on the interplay with the host imperative for their persistence. However, a lifetime of interactions conceivably have an imprint on our physiology and immune phenotype. Importantly, current metagenomics-insights on the healthy human virome are derived from bodily fluids, which are only a proxy of the true prevalence of human eukaryotic viruses within tissues. Most significantly, the virome’s systemic composition across the different organs of an individual has thus far remained uncharted. Results In this work, we revealed the genetic make-up of the eukaryotic human DNA virome in the body and showed that each organ (colon, liver, lung, heart, brain, kidney, skin, blood, hair) has unique viral compositions. By integration of quantitative (qPCR) and qualitative (hybrid-capture sequencing) analysis, we identified the DNAs of 17 viruses, primarily herpes-, parvo-, papilloma- and anello-viruses (>80% prevalence), typically persisting in low copies (mean 540 copies/ million cells). The within-sample diversities (a-diversity) were highest in the lung, liver, colon, and kidney. We assembled in total 70 viral genomes (>90% breadth coverage), distinct in each of the individuals, and identified high sequence homology across the organs. Moreover, we detected variations in virome composition and distribution in two individuals with underlying malignant conditions. Conclusions Our findings reveal unprecedented prevalences of viral DNAs in human organs. We showed that bodily fluids, although accessible to sampling, fail to deliver a comprehensive view of the numerous intracellular viruses colonizing our tissues. Our data demonstrate how a multi-organ approach is essential for analyzing differing virome compositions in various disease states. This atlas provides a fundamental ground for the studies of correlates to disease, and for the interpretation of next-generation sequencing data in clinical virology. Ultimately, our findings call for investigation of the crosstalk between human DNA viruses, the host, and other microbes, as it predictably has a significant impact on our health.

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Section: Viral Enrichment and Deep Sequencingmentioning

confidence: 99%

Unmasking the Tissue-Resident Eukaryotic DNA Virome in Humans

Pyöriä

Pratas

Toppinen

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Background Little is known on the landscape of viruses that have taken residence within our cells, nor on the interplay with the host imperative for their persistence. Yet, a lifetime of interactions conceivably have an imprint on our physiology and immune phenotype. Importantly, current metagenomics-insights on the healthy human virome are derived from bodily fluids, which are only a proxy of the true prevalence of human eukaryotic viruses within tissues. Most significantly, the virome’s systemic composition in an individual has thus far remained uncharted. Results In this work, we revealed the genetic make-up of the eukaryotic human DNA virome in the body and showed that each organ (colon, liver, lung, heart, brain, kidney, skin, blood, hair) has unique viral compositions. By integration of quantitative (qPCR) and qualitative (hybrid-capture sequencing) analysis, we identified the DNAs of 17 viruses, primarily herpes-, parvo-, papilloma- and anello-viruses (>80% prevalence), typically persisting in low copies (mean 540 copies/ million cells). The within-sample diversities (a-diversity) were highest in the lung, liver, colon, and kidney. We assembled in total 70 viral genomes (>90% breadth coverage), distinct in each of the individuals, and identified high sequence homology across the organs. Moreover, we detected variations in virome composition and distribution in two individuals with underlying malignant conditions. Conclusions Our findings reveal unprecedented prevalences of viral DNAs in human organs. We showed that bodily fluids, although accessible to sampling, fail to deliver a comprehensive view of the numerous intracellular viruses colonizing our tissues. Our data demonstrate how a multi-organ approach is essential for analyzing differing virome compositions in various disease states. This atlas provides a fundamental ground for the studies of correlates to disease, and for the interpretation of next-generation sequencing data in clinical virology. Ultimately, our findings call for investigation of the crosstalk between human DNA viruses, the host, and other microbes, as it predictably has a significant impact on our health.

show abstract

The Human Bone Marrow Is Host to the DNAs of Several Viruses

Cited by 13 publications

References 56 publications

Adverse events, side effects and complications in mesenchymal stromal cell-based therapies

Adverse events, side effects and complications in mesenchymal stromal cell-based therapies

Unmasking the Tissue-Resident Eukaryotic DNA Virome in Humans

Unmasking the Tissue-Resident Eukaryotic DNA Virome in Humans

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