Adenoviral infection in hematopoietic stem cell transplantation: early diagnosis with quantitative detection of the viral genome in serum and urine

Teramura, Tomoko; Naya, Mayumi; Yoshihara, Takao; Kanoh, G; Morimoto, Akira; Imashuku, Shinsaku

doi:10.1038/sj.bmt.1704320

Cited by 36 publications

(37 citation statements)

References 16 publications

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“…Additionally, the comprehensive sequence information would permit the establishment of highly specific detection assays covering all of the human adenovirus serotypes. Such diagnostic tests are of great importance in the surveillance of infections in immunosuppressed patients, where adenoviruses play an important role as pathogens, causing a life-threatening disease (4,20,29,30). Moreover, detailed characterization of the adenovirus hexon gene might be helpful in the context of antiviral therapy.…”

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confidence: 99%

Comparative Sequence Analysis of the Hexon Gene in the Entire Spectrum of Human Adenovirus Serotypes: Phylogenetic, Taxonomic, and Clinical Implications

Ebner

Pinsker

Lion

2005

J Virol

127

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The adenovirus (AdV) hexon constitutes the major virus capsid protein. The epitopes located on the hexon protein are targets of neutralizing antibodies in vivo, serve in the recognition by cytotoxic T cells, and provide the basis for the classification of adenoviruses into the 51 serotypes known to date. We have sequenced the entire hexon gene from human serotypes with incomplete or no sequence information available (n ‫؍‬ 34) and performed a comparative analysis of all sequences. The overall sequence divergence between the 51 human serotypes ranged from 0.7 to 25.4% at the protein level. The sequence information has been exploited to assess the phylogeny of the adenovirus family, and protein distances between the six AdV species (A to F) and among individual serotypes within each species were calculated. The analysis revealed that the differences among serotypes within individual species range from 0.3 to 5.4% in the conserved regions (765 amino acids [aa]) and from 1.5 to 59.6% in the variable regions (154 to 221 aa). Serotypes of different species showed an expectedly greater divergence both in the conserved (5.9 to 12.3%) and variable (49.0 to 74.7%) regions. Construction of a phylogenetic tree revealed three major clades comprising the species B؉D؉E, A؉F, and C, respectively. For serotypes 50 and 51, the original assignment to species B and D, respectively, is not in accordance with the hexon DNA and protein sequence data, which placed serotype 50 within species D and serotype 51 within species B. Moreover, the hexon gene of serotype 16, a member of species B, was identified as the product of recombination between sequences of species B and E. In addition to providing a basis for improved molecular diagnostics and classification, the elucidation of the complete hexon gene sequence in all AdV serotypes yields information on putative epitopes for virus recognition, which may have important implications for future treatment strategies permitting efficient targeting of any AdV serotype.Human adenoviruses (AdV) represent a large family, currently comprising 51 different serotypes, which are divided into six species (designated A to F) based on different oncogenic, hemagglutinating, morphological, and DNA sequence properties. The prevalence of AdV infections is high, as revealed by serological studies (27). The most common sites of infection in immunocompetent individuals include the gastrointestinal tract, the upper respiratory tract, and the eyes (1, 9, 22). In the presence of a functional immune system, AdV infections are not associated with life-threatening disease, but latent infections with persistence of the viral genome, involving particularly species C, have been found in about 80% of the individuals investigated (12). Adenoviruses were described to enter human cells either by the coxsackievirus and adenovirus receptor CAR (3) or by the cell surface protein CD46 (11), which are present on most human cell types (23). Since adenovirusbased vectors are not regarded as harmful to healthy individuals, they ar...

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confidence: 99%

Comparative Sequence Analysis of the Hexon Gene in the Entire Spectrum of Human Adenovirus Serotypes: Phylogenetic, Taxonomic, and Clinical Implications

Ebner

Pinsker

Lion

2005

J Virol

127

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“…Several in-house methods for adenovirus quantification in different samples have been described (4,10,12,28), and their use has been validated in different clinical situations (7,11,15,16,20,21,24,27 novirus DNA load detection or quantification using the kit assay and the in-house assay described by Heim et al (12), already in use for clinical diagnosis. qPCR assays were performed using the ABI Prism 7000 system, but the kit assay has also been validated for use with the most commonly used real-time PCR systems, including the LightCycler 530 and instruments 560 (Roche), the SmartCycler instruments (Cepheid), the ABI FAM and VIC instruments (Applied Biosystems), and the Rotor-gene Green and Yellow instruments (Corbett Research).…”

Section: Discussionmentioning

confidence: 99%

Comparison of In-House Real-Time Quantitative PCR to the Adenovirus R-Gene Kit for Determination of Adenovirus Load in Clinical Samples

Jeulin¹,

Salmon

Bordigoni

et al. 2010

J Clin Microbiol

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In the context of hematopoietic stem cell transplantation, adenovirus infections are associated with relevant mortality and morbidity. Detection of adenovirus DNA by quantitative PCR is the "gold standard" for these patients. A total of 150 samples, namely, 78 whole-blood, 22 cerebrospinal fluid, 24 digestive biopsy, and 26 stool samples, from 29 patients, including 24 hematopoietic stem cell transplant recipients, were tested for the detection of adenovirus using an in-house real-time quantitative PCR assay (A. Heim, C. Ebnet, G. Harste, and P. Pring-Akerblom, J. Med. Virol. 70:228-239, 2003) and the commercially available Adenovirus R-Gene kit. Adenovirus DNA was automatically isolated from whole-blood samples (Magna Pure LC system; Roche) or was manually extracted from other specimens (QIAamp; Qiagen) using the appropriate kit. The intra-and interassay reproducibilities and sensitivities were evaluated with cell culture supernatant dilutions. Of the 150 samples tested, 86 were found to be positive and 55 were found to be negative using both techniques. Nine (6%) discordant results were obtained. In most cases, discrepant results concerned samples with low viral loads. Quantitative results for all concordant positive samples were analyzed using the Spearman correlation test. A good correlation between the results of the in-house assay and those of the kit assay was obtained (r ‫؍‬ 0.95; P < 0.001). Regarding the threshold cycle value for internal control spiked samples, none of the 150 samples tested contained a PCR inhibitor. In conclusion, a relevant correlation of results between the in-house assay and the kit assay, as well as the high-quality reproducibility and sensitivity of the kit assay, warranted its use for follow-up of hematopoietic stem cell transplantation recipients.

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“…But studies since have shown that peripheral blood is probably the most important source for clinical surveillance of adenoviral infections in the immunocompromised setting [71,72]. A number of studies have attempted to correlate viral load to severity in order to determine when to start antiviral treatment but further work is required in order to determine whether this approach will affect patient care [73,74]. Identification of adenoviruses by species, serotypes, and strains is relevant for epidemiological studies and for a wider rationale for documentation of nosocomial outbreaks but is often not indicated in clinical practice, given the self-limited disease course.…”

Section: Workupmentioning

confidence: 99%

The Repertoire of Adenovirus in Human Disease: The Innocuous to the Deadly

Khanal¹,

Ghimire²,

Dhamoon³

2018

Preprint

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Abstract:Adenovirus is a family of double stranded DNA viruses that are a significant cause of upper respiratory tract infections in children and adults. Less commonly, the adenovirus family can cause a variety of gastrointestinal, ophthalmologic, genitourinary, and neurologic diseases. Most adenovirus infections are self-limited in the immunocompetent host and are treated with supportive measures. Fatal infections can occur in immunocompromised patients and less frequently in the healthy. Adenoviral vectors are being studied for novel biomedical applications including gene therapy and immunization. In this review we will focus on the spectrum of adenoviral infections in humans.

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Adenoviral infection in hematopoietic stem cell transplantation: early diagnosis with quantitative detection of the viral genome in serum and urine

Cited by 36 publications

References 16 publications

Comparative Sequence Analysis of the Hexon Gene in the Entire Spectrum of Human Adenovirus Serotypes: Phylogenetic, Taxonomic, and Clinical Implications

Comparative Sequence Analysis of the Hexon Gene in the Entire Spectrum of Human Adenovirus Serotypes: Phylogenetic, Taxonomic, and Clinical Implications

Comparison of In-House Real-Time Quantitative PCR to the Adenovirus R-Gene Kit for Determination of Adenovirus Load in Clinical Samples

The Repertoire of Adenovirus in Human Disease: The Innocuous to the Deadly

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