Gowen Brian B, Barnard Dale L, Smee Donald F, Wong Min-Hui, Pace Anne M, Jung Kie-Hoon, Winslow Scott G, Bailey Kevin W, Blatt Lawrence M, Sidwell Robert W
Institute for Antiviral Research, 5600 Old Main Hill, Utah State University, Logan, UT 84322, USA.
Antimicrob Agents Chemother. 2005 Jun;49(6):2378-86. doi: 10.1128/AAC.49.6.2378-2386.2005.
Hemorrhagic fever of arenaviral origin is a frequently fatal infectious disease of considerable priority to the biodefense mission. Historically, the treatment of arenaviral infections with alpha interferons has not yielded favorable results. Here we present evidence that interferon alfacon-1, a nonnaturally occurring bioengineered alpha interferon approved for the treatment of chronic hepatitis C, is active against Pichinde and Tacaribe arenaviruses in cell culture. In the hamster model of Pichinde virus (PCV) infection, interferon alfacon-1 treatment significantly protected animals from death, prolonged the survival of those that eventually died, reduced virus titers, and limited liver damage characteristic of PCV-induced disease. Moreover, interferon alfacon-1 also demonstrated therapeutic activity, to a lesser degree, when the initiation of treatment was delayed up to 2 days post-virus challenge. Despite the observed advantages of interferon alfacon-1 therapy, efforts to stimulate the immune system with the known interferon inducer poly(I:C12U) (Ampligen) offered only limited protection against lethal PCV challenge. Taken together, these data suggest that the increased potency of the bio-optimized interferon alfacon-1 molecule may be critical to the observed antiviral effects. These data are the first report demonstrating efficacious treatment of acute arenaviral disease with alpha interferon therapy, and further study is warranted.
沙粒病毒源性出血热是一种对生物防御任务至关重要的常见致命传染病。从历史上看,用α干扰素治疗沙粒病毒感染并未取得良好效果。在此,我们提供证据表明,干扰素 alfacon-1(一种被批准用于治疗慢性丙型肝炎的非天然生物工程α干扰素)在细胞培养中对皮钦德病毒和塔卡里贝沙粒病毒具有活性。在皮钦德病毒(PCV)感染的仓鼠模型中,干扰素 alfacon-1 治疗显著保护动物免于死亡,延长了最终死亡动物的存活时间,降低了病毒滴度,并限制了 PCV 诱导疾病的特征性肝损伤。此外,当治疗在病毒攻击后延迟长达 2 天开始时,干扰素 alfacon-1 也在较小程度上表现出治疗活性。尽管观察到干扰素 alfacon-1 治疗有这些优势,但用已知的干扰素诱导剂聚(I:C12U)(Ampligen)刺激免疫系统仅对致命的 PCV 攻击提供了有限的保护。综上所述,这些数据表明生物优化的干扰素 alfacon-1 分子效力的提高可能对观察到的抗病毒效果至关重要。这些数据是首次报道用α干扰素疗法有效治疗急性沙粒病毒疾病,值得进一步研究。