Metagenomic profiling of the viromes of plasma collected from blood donors with elevated serum alanine aminotransferase levels

Furuta, Rie; Sakamoto, Hirotaka; Kuroishi, Ayumu; Yasiui, Kazuta; Matsukura, Harumichi; Hirayama, Fumiya

doi:10.1111/trf.13057

Cited by 32 publications

(29 citation statements)

References 48 publications

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“…They suggested that ALT can be a useful marker for the detection of HCV-infected donors in whom technical problems may have occurred during serological screening. Furuta et al [26] collected disqualified donors' plasma with ALT levels of >60 IU/L, even if they were serologically negative for TTIs, to assess the potential risk of TTIs by metagenomic analysis of virome profiles. The typical TTIs were all negative, suggesting that serum ALT testing may be unsuitable for monitoring the additional risks of TTIs in blood donors who are negative for typical TTIs using serologic tests and NATs.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Occult Hepatitis C Virus Infection among Blood Donors in Jiangsu, China

Lin

Chen²,

Zhu³

et al. 2016

Intervirology

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Objective: In 2010, only 1 donor blood sample was found to be anti-hepatitis C virus (HCV) negative and HCV RNA positive, as detected by nucleic acid testing. In occult HCV infection (OCI), HCV RNA is found in peripheral blood mononuclear cells (PBMCs). We investigated the prevalence of OCI among blood donors. Methods: We collected 513 samples from 334 eligible and 179 deferred donors, including 55 anti-HCV-positive, 113 alanine aminotransferase (ALT)-elevated, and 11 hepatitis B virus surface antigen (HBsAg)-positive blood donors. PBMCs were isolated, the 5′-untranslated region of HCV RNA was amplified by reverse transcription nested PCR, and the genotype of the core region was determined. Results: No HCV RNA was detected among the eligible samples. Among the deferred donors, 15 (27.2%) had detectable HCV RNA in 55 anti-HCV PBMC specimens. HCV RNA was detected in 1 (9.1%) HBsAg-positive and 9 (8%) ALT-elevated samples. The prevalence of OCI in the blood donors was 2.2% (10/458). HCV genotypes were determined in 10 subjects, indicating that 2 (20.0%) were subtype 2a, 7 (70.0%) were 1b, and 1 (10%) was 6a. Conclusions: This study showed that OCI does exist among Chinese blood donors. However, to determine the epidemiology and outcome of this HCV infection, further follow-up with more participants and patients receiving blood components with OCI is needed.

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Section: Discussionmentioning

confidence: 99%

Prevalence of Occult Hepatitis C Virus Infection among Blood Donors in Jiangsu, China

Lin

Chen²,

Zhu³

et al. 2016

Intervirology

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“…The study of the human virome is particularly relevant in the context of current discussions of next-generation sequencing for surveillance of viruses in blood and for transfusion safety [11, 15, 16]. Only viruses that are both pathogenic and transfusion-transmissible are routinely tested for and excluded from blood-derived products.…”

Section: Introductionmentioning

confidence: 99%

The blood DNA virome in 8,000 humans

Moustafa¹,

Xie²,

Kirkness³

et al. 2017

PLoS Pathog

268

258

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The characterization of the blood virome is important for the safety of blood-derived transfusion products, and for the identification of emerging pathogens. We explored non-human sequence data from whole-genome sequencing of blood from 8,240 individuals, none of whom were ascertained for any infectious disease. Viral sequences were extracted from the pool of sequence reads that did not map to the human reference genome. Analyses sifted through close to 1 Petabyte of sequence data and performed 0.5 trillion similarity searches. With a lower bound for identification of 2 viral genomes/100,000 cells, we mapped sequences to 94 different viruses, including sequences from 19 human DNA viruses, proviruses and RNA viruses (herpesviruses, anelloviruses, papillomaviruses, three polyomaviruses, adenovirus, HIV, HTLV, hepatitis B, hepatitis C, parvovirus B19, and influenza virus) in 42% of the study participants. Of possible relevance to transfusion medicine, we identified Merkel cell polyomavirus in 49 individuals, papillomavirus in blood of 13 individuals, parvovirus B19 in 6 individuals, and the presence of herpesvirus 8 in 3 individuals. The presence of DNA sequences from two RNA viruses was unexpected: Hepatitis C virus is revealing of an integration event, while the influenza virus sequence resulted from immunization with a DNA vaccine. Age, sex and ancestry contributed significantly to the prevalence of infection. The remaining 75 viruses mostly reflect extensive contamination of commercial reagents and from the environment. These technical problems represent a major challenge for the identification of novel human pathogens. Increasing availability of human whole-genome sequences will contribute substantial amounts of data on the composition of the normal and pathogenic human blood virome. Distinguishing contaminants from real human viruses is challenging.

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“…In addition, this approach allows for the detection of variants of known viruses or synthetic viral agents, which may not be recognized by PCR or serological based techniques. One limitation of this strategy is that viral sequences are present at very low levels relative to host sequences in clinical samples, which limits the sensitivity of viral detection and the ability to reconstruct viral genomes [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

dsRNA-Seq: Identification of viral infection by purifying and sequencing dsRNA

Decker

Steiner²,

Hoon-Hanks

et al. 2019

Preprint

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RNA viruses are a major source of emerging and re-emerging infectious diseases around the world. We developed a method to identify RNA viruses that is based on the fact that all RNA viruses produce dsRNA while replicating. Purifying and sequencing dsRNA from total RNA isolated from infected tissue allowed us to recover replicating viral sequences. We refer to this approach as dsRNA-Seq. By assembling dsRNA sequences into contigs we identified full length RNA viruses of varying genome types infecting mammalian culture samples, identified a known viral disease agent in laboratory infected mice, and successfully detected naturally occurring RNA viral infections in reptiles. Here we show that dsRNA-Seq is a preferable method for identifying viruses in organisms that don't have sequenced genomes and/or commercially available rRNA depletion reagents.Similar to other metagenomic strategies, dsRNA-Seq has the potential to identify unknown viral disease agents that share little to no similarity to known viruses. However, the significant advantage of this method is the ability to identify replicated viral sequences, which is useful for distinguishing infectious viral agents from potential noninfectious viral particles or contaminants.

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Metagenomic profiling of the viromes of plasma collected from blood donors with elevated serum alanine aminotransferase levels

Abstract: The serum ALT test may be unsuitable for monitoring for additional risks of TTIs in blood donors who were negative for typical TTIs using serologic and nucleic acid tests. Although MGA is less sensitive than PCR, it remains the best technology to detect known viruses in these donors.

Cited by 32 publications

References 48 publications

Prevalence of Occult Hepatitis C Virus Infection among Blood Donors in Jiangsu, China

Prevalence of Occult Hepatitis C Virus Infection among Blood Donors in Jiangsu, China

The blood DNA virome in 8,000 humans

dsRNA-Seq: Identification of viral infection by purifying and sequencing dsRNA

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