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Arsenic trioxide influences viral replication in target organs of coxsackievirus B3-infected mice
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. (Infektionssjukdomar)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Enheten för metallbiologisk forskning.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Bacteriology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
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2010 (English)In: Microbes and infection, ISSN 1286-4579, E-ISSN 1769-714X, Vol. 12, no 12-13, 1027-1034 p.Article in journal (Refereed) Published
Abstract [en]

New antiviral agents are urgently needed. Based on in vitro studies, arsenic trioxide (As2O3) seems to affect viral replication, although this has been studied only marginally in vivo. In this study the replication of coxsackievirus B3 (CVB3) was studied in Balb/c mice administered 1 mg As2O3/kg bw once daily during 7 days of infection and in Vero cells exposed for 3 or 5 days to 0.4, 2 or 4 µM As2O3. Viral RNA was measured by reverse-transcription PCR (RT-PCR) (in vitro and in vivo) and arsenic concentration was measured by inductively coupled plasma-mass spectrometry (ICP-MS) (in vivo). In vivo, As2O3 decreased viral RNA in the brain on days 3 (by 81%; p<0.05) and 7 (by 97%; p<0.01) and in the pancreas on day 7 (by 75%; p<0.05), two of the target organs of this infection. The results were confirmed in vitro, where As2O3 dose-dependently reduced viral RNA, with the effect being more pronounced in the surrounding culture medium than inside the infected cells, indicating an impaired virion release. Thus, As2O3 reduced CVB3 replication both in vitro and in vivo, indicating that As2O3 is a viable option in the pursuit of new therapeutic agents against viral infections.

Place, publisher, year, edition, pages
2010. Vol. 12, no 12-13, 1027-1034 p.
Keyword [en]
arsenic trioxide, Coxsackie virus B3, virus replication, tissue, mice
National Category
Medical and Health Sciences
Research subject
Infectious Diseases
Identifiers
URN: urn:nbn:se:uu:diva-112043DOI: 10.1016/j.micinf.2010.07.003ISI: 000284434800016PubMedID: 20638482OAI: oai:DiVA.org:uu-112043DiVA: diva2:284474
Available from: 2010-01-07 Created: 2010-01-07 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Arsenic Influences Virus Replication in Experimental Coxsackievirus B3 Infection
Open this publication in new window or tab >>Arsenic Influences Virus Replication in Experimental Coxsackievirus B3 Infection
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Trace elements are essential for the host defence against infections, and during common infections, the balance of trace elements is changed in serum and tissues. Supplementation with selenium (Se), an essential trace element, is known to decrease the severity of coxsackievirus B3 (CVB3) infection in mice. Even the non-essential trace element arsenic (As) seems to influence the replication of some viruses.

During the course of an acute CVB3 infection in mice, Se concentrations decreased in most tissues and were negatively correlated to viral load in our study. However, As concomitantly decreased in most tissues. As has previously been shown to interfere with the balance of essential trace elements. However, in the present study As supplementation in healthy mice resulted in minor effects on seven studied trace elements in serum and tissues. The effects of As supplementation were more pronounced in CVB3-infected mice, with an increase in As, but a decrease in Se in most tissues when compared with non-infected mice.

As supplementation during CVB3 infection in mice decreased viral RNA concentrations in the brain (97%) and pancreas (75%), two of the target organs of this infection. In vitro experiments indicate that As caused an impaired virion assembly or release. In vivo, infection-induced expression of the host defence-associated genes nuclear factor κB (NFκB) and interferon γ (IFN-γ) were unaffected by As supplementation, except for an earlier increase in IFN-γ in the brain.

In conclusion, a clinically relevant dose of As decreased the replication of CVB3 in vitro and in vivo. This antiviral effect in vivo was not related to changes in specific trace elements or in the host’s immune-mediated defence. Although the mechanism underlying the observed effect on viral replication remains to be further elucidated, As seems to be an intriguing trace element to study in the pursuit of new antiviral drugs.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 66 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 513
Keyword
coxsackievirus B3, trace elements, arsenic, selenium, virology, IFN-γ, NFκB
National Category
Infectious Medicine
Research subject
Infectious Diseases
Identifiers
urn:nbn:se:uu:diva-112049 (URN)978-91-554-7702-8 (ISBN)
Public defence
2010-02-19, Hörsalen, Klinisk mikrobiologi, Akademiska sjukhuset, ingång D1, Dag Hammarskjölds väg 17, Uppsala, 13:15 (Swedish)
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Supervisors
Available from: 2010-01-28 Created: 2010-01-07 Last updated: 2010-01-28Bibliographically approved

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