Alidjinou Enagnon Kazali, Sané Famara, Bertin Antoine, Caloone Delphine, Hober Didier
Université Lille 2, Faculté de Médecine, CHRU de Lille, Laboratoire de virologie EA3610, Lille, France.
Université Lille 2, Faculté de Médecine, CHRU de Lille, Laboratoire de virologie EA3610, Lille, France.
Antiviral Res. 2015 Apr;116:51-4. doi: 10.1016/j.antiviral.2015.01.010. Epub 2015 Feb 2.
Group B Coxsackieviruses (CVB) are involved in various acute clinical features and they can play a role in the development of chronic diseases like type 1 diabetes. The persistence of CVB has been described in vitro and in vivo in various models. Fluoxetine was reported to inhibit the replication of CVB1-3, which prompted us to study the in vitro antiviral activity of fluoxetine against CVB4 in models of acute infection. In addition we took advantage of a chronically CVB4-infected Panc-1 cell line to evaluate the antiviral effect of fluoxetine in a model of persistent CVB4 infection. An inhibition of the CVB4 replication was obtained when fluoxetine was added at 5.48μM to Hep-2 cell cultures. No inhibitory effect was observed when CVB4 was mixed with fluoxetine for 2h and filtered to eliminate fluoxetine before inoculation to cells, or when cells were treated up to 96h and washed before viral inoculation. Fluoxetine (5.48μM) reduced viral replication by more than 50% in acutely infected Panc-1 cell cultures. A dramatic decrease of infectious particles levels in supernatants of Panc-1 cells chronically infected with CVB4 was obtained a few days after treatment with fluoxetine and no infectious viral particle was found as soon as day 21 of treatment, and intracellular enteroviral RNA was undetectable by RT-PCR after three weeks of treatment. These data display that fluoxetine can inhibit the replication of CVB4 and can cure Panc-1 cells chronically infected with CVB4.
B组柯萨奇病毒（CVB）与多种急性临床特征有关，并且在1型糖尿病等慢性疾病的发展中可能起作用。CVB在体外和体内的各种模型中均有持续性感染的报道。据报道，氟西汀可抑制CVB1 - 3的复制，这促使我们在急性感染模型中研究氟西汀对CVB4的体外抗病毒活性。此外，我们利用长期感染CVB4的Panc - 1细胞系来评估氟西汀在持续性CVB4感染模型中的抗病毒作用。当向Hep - 2细胞培养物中添加5.48μM氟西汀时，可抑制CVB4的复制。当CVB4与氟西汀混合2小时并过滤以去除氟西汀后再接种到细胞中，或者在接种病毒前对细胞进行长达96小时的处理并洗涤时，未观察到抑制作用。在急性感染的Panc - 1细胞培养物中，氟西汀（5.48μM）可使病毒复制减少50%以上。在用氟西汀治疗几天后，长期感染CVB4的Panc - 1细胞培养上清液中的感染性颗粒水平显著下降，在治疗第21天时就未发现感染性病毒颗粒，并且在治疗三周后通过RT - PCR检测不到细胞内肠道病毒RNA。这些数据表明，氟西汀可抑制CVB4的复制，并可治愈长期感染CVB4的Panc - 1细胞。
