Oral ribavirin for severe adenovirus infection after allogeneic marrow transplantation

Abe, Shunsuke; Miyamura, Koichi; Oba, Taku; Terakura, Seitaro; Kasai, Masanobu; Kitaori, K; Sasaki, Takeshi; Kodera, Yoshihisa

doi:10.1038/sj.bmt.1704276

Cited by 30 publications

(17 citation statements)

References 8 publications

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“…In general, adenoviruses cause self-limiting infections of the eye, or gastrointestinal and respiratory tract, which can lead to epidemic keratoconjunctivitis, diarreah, and severe acute respiratory diseases [1]–[9]. However, with increasing prevalence of transplantations with concomittant downregulation of the immune system (such as in bone marrow transplations), the frequency of disseminated adenoviral infections is also rising in immuno-compromised patients, resulting in high mortality rates [10], [11]. Unfortunately, no specified antiviral treatments or wide-spread vaccination strategies are currently available to counteract adenoviral outbreaks in an efficient manner [12], [13].…”

Section: Introductionmentioning

confidence: 99%

A Ubiquitin-specific Protease Possesses a Decisive Role for Adenovirus Replication and Oncogene-mediated Transformation

et al. 2013

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Adenoviral replication depends on viral as well as cellular proteins. However, little is known about cellular proteins promoting adenoviral replication. In our screens to identify such proteins, we discovered a cellular component of the ubiquitin proteasome pathway interacting with the central regulator of adenoviral replication. Our binding assays mapped a specific interaction between the N-terminal domains of both viral E1B-55K and USP7, a deubiquitinating enzyme. RNA interference-mediated downregulation of USP7 severely reduced E1B-55K protein levels, but more importantly negatively affected adenoviral replication. We also succeeded in resynthesizing an inhibitor of USP7, which like the knockdown background reduced adenoviral replication. Further assays revealed that not only adenoviral growth, but also adenoviral oncogene-driven cellular transformation relies on the functions of USP7. Our data provide insights into an intricate mechanistic pathway usurped by an adenovirus to promote its replication and oncogenic functions, and at the same time open up possibilities for new antiviral strategies.

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Section: Introductionmentioning

confidence: 99%

A Ubiquitin-specific Protease Possesses a Decisive Role for Adenovirus Replication and Oncogene-mediated Transformation

et al. 2013

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“…Analysis of HAdV isolates revealed a consistent sensitivity of all types belonging to species C only (224), and the evidence for therapeutic efficacy of the compound in vivo is controversial (225,(230)(231)(232)(233). Ribavirin is therefore not generally recommended for treatment of HAdV infections (143,234).…”

Section: Antiviral Drugsmentioning

confidence: 99%

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

2014

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SUMMARY Human adenoviruses (HAdVs) are an important cause of infections in both immunocompetent and immunocompromised individuals, and they continue to provide clinical challenges pertaining to diagnostics and treatment. The growing number of HAdV types identified by genomic analysis, as well as the improved understanding of the sites of viral persistence and reactivation, requires continuous adaptions of diagnostic approaches to facilitate timely detection and monitoring of HAdV infections. In view of the clinical relevance of life-threatening HAdV diseases in the immunocompromised setting, there is an urgent need for highly effective treatment modalities lacking major side effects. The present review summarizes the recent progress in the understanding and management of HAdV infections.

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“…40 In contrast with what may be expected, there are several case reports suggesting therapeutic benefit for some patients with no response reported in others. [41][42][43] Because of availability of the more effective cidofovir, it is not included in our guideline. Although less efficient than nucleotide analogues, ganciclovir can be tri-phosphorylated by cellular kinases which results in interference with the function of AdV DNA polymerase, thus inhibiting viral replication in vitro.…”

Section: Antiviral Drugsmentioning

confidence: 99%