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Published on: July 15, 2019
Arsenic trioxide influences viral replication in target organs of coxsackievirus B3-infected mice
Ylva Molin1, Peter Frisk, Eva Hjelm
1Infectious Diseases, Department of Medical Sciences, Uppsala University Hospital, S-751 85 Uppsala, Sweden. ylva.molin@medsci.uu.se
Abstract:
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.
Insights
Arsenic trioxide (As₂O₃) effectively reduced coxsackievirus B3 (CVB3) replication in mice and cell cultures. This study highlights As₂O₃ as a potential therapeutic agent for viral infections.
Area of Science:
- Virology
- Pharmacology
- Toxicology
Background:
- New antiviral agents are crucial for public health.
- Arsenic trioxide (As₂O₃) has shown potential antiviral activity in vitro.
- In vivo studies on As₂O₃ for viral infections are limited.
Purpose of the Study:
- To investigate the in vivo and in vitro efficacy of As₂O₃ against coxsackievirus B3 (CVB3) replication.
- To determine the effect of As₂O₃ on viral RNA levels in target organs and cell cultures.
- To explore the mechanism of As₂O₃'s antiviral action.
Main Methods:
- Balb/c mice were treated daily with As₂O₃ during CVB3 infection.
- Vero cells were exposed to varying concentrations of As₂O₃.
- Viral RNA was quantified using reverse transcription PCR (RT-PCR).
- Arsenic levels were measured using inductively coupled plasma-mass spectrometry (ICP-MS).
Main Results:
- In vivo, As₂O₃ significantly reduced CVB3 RNA in the brain and pancreas.
- In vitro, As₂O₃ demonstrated a dose-dependent reduction in viral RNA.
- The antiviral effect was more pronounced in the culture medium, suggesting impaired virion release.
Conclusions:
- As₂O₃ effectively inhibits CVB3 replication both in vivo and in vitro.
- As₂O₃ shows promise as a therapeutic candidate for viral infections.
- Further research into As₂O₃ as an antiviral agent is warranted.
