ATO (Arsenic Trioxide) effects on promyelocytic leukemia nuclear bodies reveals antiviral intervention capacity

Abstract: Human adenoviruses (HAdV) are associated with clinical symptoms such as gastroenteritis, keratoconjunctivitis, pneumonia, hepatitis, and encephalitis. In the absence of protective immunity, as in allogeneic bone marrow transplant patients, HAdV infections can become lethal. Alarmingly, various outbreaks of highly pathogenic, pneumotropic HAdV types have been recently reported, causing severe and lethal respiratory diseases. Effective drugs for treatment of HAdV infections are still lacking. The repurposing of drugs approved for other indications is a valuable alternative for the development of new antiviral therapies and is less risky and costly than de novo development. Arsenic trioxide (ATO) is approved for treatment of acute promyelocytic leukemia. Here, it is shown that ATO is a potent inhibitor of HAdV. ATO treatment blocks virus expression and replication by reducing the number and integrity of promyelocytic leukemia (PML) nuclear bodies, important subnuclear structures for HAdV replication. Modification of HAdV proteins with small ubiquitin-like modifiers (SUMO) is also key to HAdV replication. ATO reduces levels of viral SUMO-E2A protein, while increasing SUMO-PML, suggesting that ATO interferes with SUMOylation of proteins crucial for HAdV replication. It is concluded that ATO targets cellular processes key to HAdV replication and is relevant for the development of antiviral intervention strategies

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch
Notes
ISSN: 2198-3844

Event
Veröffentlichung
(where)
Freiburg
(who)
Universität
(when)
2023
Creator
Hofmann, Samuel
Mai, Julia
Masser, Sawinee
Groitl, Peter
Herrmann, Alexander Frank
Sternsdorf, Thomas
Brack‐Werner, Ruth
Schreiner, Sabrina

DOI
10.1002/advs.201902130
URN
urn:nbn:de:bsz:25-freidok-2391025
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
14.08.2025, 10:45 AM CEST

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Associated

Time of origin

  • 2023

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