Detection and Quantitation of Subgroup C Adenovirus DNA in Human Tissue Samples by Real-Time PCR

Garnett, C. T.; Pao, Ching-I; Gooding, Linda R.

doi:10.1385/1-59745-166-5:193

Cited by 8 publications

(10 citation statements)

References 12 publications

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“…This condition may well represent specific characteristics of virus pathogenesis regarding the mode of infection and reactivation. The persistence of adenovirus species C, demonstrated by the presence of DNA in T lymphocytes from tonsils, is higher in younger age groups (37).…”

Section: Discussionmentioning

confidence: 95%

“…The pediatric population may be more vulnerable because they are more likely to experience either primary infections or reactivation. Larger quantities of adenovirus DNA from species C were detected in tonsils from children of less than 9 years old than in those from older children (37). The higher occurrence of adenovirus reactivation could be due to the discontinuation of the once widespread practice of tonsillectomy and adenotomy in young children.…”

Section: Adenoviruses In Acquired Immunodeficiency Bmt and Hsct Recipmentioning

confidence: 97%

“…This is particularly observed for species C. Serotypes 1, 2, and 5 persist in tonsils for years through low-grade replication. Specifically, T lymphocytes in tonsils and adenoids may harbor adenovirus DNA (37). This condition may represent specific characteristics of virus pathogenesis, such as the mode of infection and reactivation.…”

Section: Latency/persistencementioning

confidence: 99%

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Adenoviruses in Immunocompromised Hosts

2008

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SUMMARY The number of patients with acquired immunodeficiency has grown steadily as a result of both a larger number of patients receiving solid organ and hematopoietic stem cell transplants and their longer survival times. The use of newer, more potent immunosuppressive regimens has increased the frequency of severe adenovirus infections. Human adenoviruses are a large group of viruses, represented by at least 52 serotypes with various genotypes divided into genomic clusters, and these may cause a broad variety of clinical manifestations. The development of molecular methods has increased the sensitivity and rapidity of adenovirus infection diagnosis. The implementation of PCR assays has significantly contributed to the identification of patients with disseminated adenovirus disease. More recently, the development of real-time PCR assays has permitted virus quantification and patient follow-up. There is no treatment for adenovirus with demonstrated efficacy, although cidofovir is widely used. Sensitive diagnostic tests for adenovirus can contribute to the early diagnosis and successful treatment of life-threatening adenovirus infections, especially in complex immunocompromised patients. The development of improved adenovirus therapy still remains a challenge. Adenovirus genetic diversity should be considered for diagnosis, typing, and therapeutic interventions.

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Section: Discussionmentioning

confidence: 95%

Section: Adenoviruses In Acquired Immunodeficiency Bmt and Hsct Recipmentioning

confidence: 97%

Section: Latency/persistencementioning

confidence: 99%

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Adenoviruses in Immunocompromised Hosts

2008

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“…Quantitative real-time PCR was performed with an ABI 7700 instrument (Applied Biosciences, Forest City, CA) and with the PerFeCTa qPCR FastMix (Quanta Biosciences, Gaithersburg, MD) according to the manufacturer's directions. Forward and reverse primers specific for the hexon gene of adenovirus were used in conjunction with a fluorescent probe to this same region (23). The amplification profile used was as follows: 1 cycle at 95C for 10 min and 50 cycles at 95°C for 15 s and 55°C for 1 min.…”

Section: Methodsmentioning

confidence: 99%

Widespread Phosphorylation of Histone H2AX by Species C Adenovirus Infection Requires Viral DNA Replication

Nichols

Schaack

Ornelles

2009

J Virol

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Adenovirus infection activates cellular DNA damage response and repair pathways. Viral proteins that are synthesized before viral DNA replication prevent recognition of viral genomes as a substrate for DNA repair by targeting members of the sensor complex composed of Mre11/Rad50/NBS1 for degradation and relocalization, as well as targeting the effector protein DNA ligase IV. Despite inactivation of these cellular sensor and effector proteins, infection results in high levels of histone 2AX phosphorylation, or γH2AX. Although phosphorylated H2AX is a characteristic marker of double-stranded DNA breaks, this modification was widely distributed throughout the nucleus of infected cells and was coincident with the bulk of cellular DNA. H2AX phosphorylation occurred after the onset of viral DNA replication and after the degradation of Mre11. Experiments with inhibitors of the serine-threonine kinases ataxia telangiectasia mutated (ATM), AT- and Rad3-related (ATR), and DNA protein kinase (DNA-PK), the kinases responsible for H2AX phosphorylation, indicate that H2AX may be phosphorylated by ATR during a wild-type adenovirus infection, with some contribution from ATM and DNA-PK. Viral DNA replication appears to be the stimulus for this phosphorylation event, since infection with a nonreplicating virus did not elicit phosphorylation of H2AX. Infected cells also responded to high levels of input viral DNA by localized phosphorylation of H2AX. These results are consistent with a model in which adenovirus-infected cells sense and respond to both incoming viral DNA and viral DNA replication.

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“…They persist focally in tonsils for years through low-grade replication. Surprisingly, T lymphocytes in tonsils and adenoids may harbor adenovirus-DNA (Garnett et al, 2007). This suggests that endogenous reactivation may occur during periods of immunosuppression after stem cell transplantation.…”

Section: Serotypes Of Adenoviruses Inducing Cystitis and Acute Renal mentioning

confidence: 99%