Arsenic trioxide influences viral replication in target organs of coxsackievirus B3-infected mice

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.