Adenovirus infections in immuncompromised patients

Stercz, Balázs; Nagy, K.; Ongrádi, J

doi:10.1556/oh.2012.29496

Cited by 9 publications

(5 citation statements)

References 71 publications

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“…But HAdV7, a member of the B1 subspecies, has been identified in epidemics to be highly virulent and is associated with clinical manifestations of considerable severity, including residual lung damage and fatal outcomes (8–10). This pathogen has been found in outbreaks in the United States and Asia and has become a global concern (11–13).…”

Section: Genome Announcementmentioning

confidence: 99%

Complete Genome Sequence of Human Adenovirus Type 7 Associated with Fatal Infant Pneumonia

Tang

et al. 2013

Genome Announc

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Section: Genome Announcementmentioning

confidence: 99%

Complete Genome Sequence of Human Adenovirus Type 7 Associated with Fatal Infant Pneumonia

Tang

et al. 2013

Genome Announc

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“…Some serotypes can cause serious ocular illness such as epidemic keratoconjunctinitis. In immunocompromised individuals, especially in pediatric hematopoietic stem cell transplant patients, Ads can cause severe disseminated multi-organ infections which are sometimes lethal ( Echavarria, 2008 , Ison, 2006 , Lion, 2014 , Matthes-Martin et al, 2012 , Matthes-Martin et al, 2013 , Sandkovsky et al, 2014 , Stercz et al, 2012 , Wold and Ison, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Transcriptome sequencing and development of an expression microarray platform for liver infection in adenovirus type 5-infected Syrian golden hamsters

et al. 2015

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The Syrian golden hamster is an attractive animal for research on infectious diseases and other diseases. We report here the sequencing, assembly, and annotation of the Syrian hamster transcriptome. We include transcripts from ten pooled tissues from a naïve hamster and one stimulated with lipopolysaccharide. Our data set identified 42,707 non-redundant transcripts, representing 34,191 unique genes. Based on the transcriptome data, we generated a custom microarray and used this new platform to investigate the transcriptional response in the Syrian hamster liver following intravenous adenovirus type 5 (Ad5) infection. We found that Ad5 infection caused a massive change in regulation of liver transcripts, with robust up-regulation of genes involved in the antiviral response, indicating that the innate immune response functions in the host defense against Ad5 infection of the liver. The data and novel platforms developed in this study will facilitate further development of this important animal model.

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“…These patients, unlike immunocompetent ones, cannot clear the virus infection, and thus, it can develop into a multiorgan or generalized disease. Especially at risk are pediatric allogeneic hematopoietic stem cell transplant (HSCT) patients, in which the incidence of Ad infection is between 3 and 47% and the mortality rate is considerable (3,(5)(6)(7)(8)(9)(10). In allogeneic HSCT patients with a rising load of Ad in peripheral blood (as determined by quantitative PCR [qPCR]), despite antiviral therapy, mortality can approach 100% (9).…”

mentioning

confidence: 99%

Ganciclovir Inhibits Human Adenovirus Replication and Pathogenicity in Permissive Immunosuppressed Syrian Hamsters

Bai

Tollefson

Spencer

et al. 2014

Antimicrob Agents Chemother

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Adenovirus infections of immunocompromised patients can develop into deadly multiorgan or systemic disease. The virus is especially threatening for pediatric allogeneic hematopoietic stem cell transplant recipients; according to some studies, 10% or more of these patients succumb to disease resulting from adenovirus infection. At present, there is no drug approved for the treatment or prevention of adenovirus infections. Compounds that are approved to treat other virus infections are used off-label to combat adenovirus, but only anecdotal evidence of the efficacy of these drugs exists. Ganciclovir, a drug approved for the treatment of herpesvirus infection, was previously reported to be effective against human adenoviruses in vitro. To model adenovirus infections in immunocompromised humans, we examined ganciclovir's efficacy in immunosuppressed Syrian hamsters intravenously infected with type 5 human adenovirus (Ad5). This animal model is permissive for Ad5 replication, and the animals develop symptoms similar to those seen in humans. We demonstrate that ganciclovir suppresses Ad5 replication in the liver of infected hamsters and that it mitigates the consequences of Ad5 infections in these animals when administered prophylactically or therapeutically. We show that ganciclovir inhibits Ad5 DNA synthesis and late gene expression. The mechanism of action for the drug is not clear; preliminary data suggest that it exerts its antiadenoviral effect by directly inhibiting the adenoviral DNA polymerase. While more extensive studies are required, we believe that ganciclovir is a promising drug candidate to treat adenovirus infections. Brincidofovir, a drug with proven activity against Ad5, was used as a positive control in the prophylactic experiment.

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Adenovirus infections in immuncompromised patients

Cited by 9 publications

References 71 publications

Complete Genome Sequence of Human Adenovirus Type 7 Associated with Fatal Infant Pneumonia

Complete Genome Sequence of Human Adenovirus Type 7 Associated with Fatal Infant Pneumonia

Transcriptome sequencing and development of an expression microarray platform for liver infection in adenovirus type 5-infected Syrian golden hamsters

Ganciclovir Inhibits Human Adenovirus Replication and Pathogenicity in Permissive Immunosuppressed Syrian Hamsters

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