Interferon alfacon-1 protects hamsters from lethal Pichinde virus infection
Interferon alfacon-1 protects hamsters from lethal Pichinde virus infection
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DOI：
10.1128/aac.49.6.2378-2386.2005
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发表时间：
2005-06-01
影响因子：
4.9
通讯作者：
Sidwell, RW
中科院分区：
文献类型：
--
作者：
Gowen, BB;Barnard, DL;Sidwell, RW
起源于阿拉伯病毒的出血热是一种经常致命的传染病，对生物防御任务具有相当高的优先级。从历史上看，用α干扰素治疗呼吸道病毒感染并没有产生良好的效果。在这里，我们提出的证据表明，干扰素alfacon-1，一种非天然存在的生物工程α干扰素，被批准用于治疗慢性丙型肝炎，在细胞培养中对Pichinde和Tacaribe arenav病毒具有活性。在Pichinde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，延长最终死亡动物的生存时间，降低病毒滴度，并限制PCV诱导疾病的肝脏损害。此外，当开始治疗推迟到病毒攻击后2天时，干扰素α-1也在较小程度上显示出治疗活性。尽管观察到干扰素α-1治疗的优势，但用已知的干扰素诱导剂聚(I：C12U)(Ampligen)刺激免疫系统的努力对致命的PCV攻击只能提供有限的保护。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是观察到的抗病毒效果的关键。这些数据是第一份证明用α干扰素治疗急性病毒性疾病有效的报告，进一步的研究是有必要的。
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.