title: 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.
authors.affiliation: Infectious Diseases, Department of Medical Sciences, Uppsala University Hospital, S-751 85 Uppsala, Sweden. ylva.molin@medsci.uu.se
authors.forename: Ylva
authors.initials: Y
authors.lastname: Molin
authors.forename: Peter
authors.initials: P
authors.lastname: Frisk
authors.forename: Eva
authors.initials: E
authors.lastname: Hjelm
authors.forename: Jonas
authors.initials: J
authors.lastname: Blomberg
authors.forename: Göran
authors.initials: G
authors.lastname: Friman
authors.forename: Nils-Gunnar
authors.initials: NG
authors.lastname: Ilbäck
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001921:Brain / Q000821:virology; D002522:Chlorocebus aethiops; D003384:Coxsackievirus Infections / Q000188:drug therapy* / Q000821:virology; D004305:Dose-Response Relationship, Drug; D029822:Enterovirus B, Human / Q000187:drug effects*; D005260:Female; D013058:Mass Spectrometry; D051379:Mice; D008807:Mice, Inbred BALB C; D010087:Oxides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D010179:Pancreas / Q000821:virology; D010949:Plasma / Q000737:chemistry; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D001152:Arsenicals; D010087:Oxides; D012367:RNA, Viral; D000077237:Arsenic Trioxide