治疗性利用病毒干扰。

StephenW

Infect Disord Drug Targets. 2019 Apr 5. doi: 10.2174/1871526519666190405140858. [Epub ahead of print]
Therapeutic exploitation of viral interference.
Kovesdi I1, Bakacs T2.
Author information

1
    ImiGene, Inc., Rockville, MD. United States.
2
    HepC, Inc., Budapest. Hungary.

Abstract

Viral interference, originally, referred to a state of temporary immunity, whereby infection with a virus limits replication or production of a second infecting virus. However, replication of a second virus could also be dominant over the first virus. In fact, dominance can alternate between the two viruses. Expression of type I interferon genes is many times upregulated in infected epithelial cells. Since the interferon system can control most, if not all, virus infections in the absence of adaptive immunity, it was proposed that viral induction of a nonspecific localized temporary state of immunity may provide a strategy to control viral infections. Clinical observations also support such a theory, which gave credence to the development of superinfection therapy (SIT). SIT is an innovative therapeutic approach where a non-pathogenic virus is used to infect patients harboring a pathogenic virus. For the functional cure of persistent viral infections and for the development of broad spectrum antivirals against emerging viruses a paradigm shift was recently proposed. Instead of the virus, the therapy should be directed at the host. Such a host-directed-therapy (HDT) strategy could be the activation of endogenous innate immune response via toll-like receptors (TLRs). Superinfection therapy is such a host-directed-therapy, which has been validated in patients infected with two completely different viruses, the hepatitis B (DNA), and hepatitis C (RNA) viruses. SIT exerts post-infection interference via the constant presence of an attenuated non-pathogenic avian double stranded (ds) RNA viral vector which boosts the endogenous innate (IFN) response. SIT could therefore be developed into a biological platform for a new "one drug, multiple bugs" broad-spectrum antiviral treatment approach.

Copyright© Bentham Science Publishers; For any queries, please email at [email protected].
KEYWORDS:

; Viral interference; antiviral gene responses; dsRNA virus; pandemic preparedness; persistent HBV infection; viral superinfection

PMID:
    30950360
DOI:
    10.2174/1871526519666190405140858

StephenW

感染Disord药物目标。 2019年4月5日：doi：10.2174 / 1871526519666190405140858。 [印刷前的电子版]
治疗性利用病毒干扰。
Kovesdi I1，Bakacs T2。
作者信息

1
    ImiGene，Inc.，Rockville，MD。美国。
2
    HepC，Inc.，布达佩斯。匈牙利。

抽象

最初，病毒干扰是指临时免疫状态，其中病毒感染限制了第二种感染病毒的复制或产生。然而，第二种病毒的复制也可能比第一种病毒占优势。事实上，优势可以在两种病毒之间交替。 I型干扰素基因的表达在感染的上皮细胞中多次上调。由于干扰素系统可以在没有适应性免疫的情况下控制大多数（如果不是全部）病毒感染，因此提出病毒诱导非特异性局部临时免疫状态可以提供控制病毒感染的策略。临床观察也支持这样的理论，这使得重叠感染疗法（SIT）的发展得到了证实。 SIT是一种创新的治疗方法，其中非病原性病毒用于感染携带病原性病毒的患者。对于持续性病毒感染的功能性治愈和针对新出现的病毒的广谱抗病毒药物的开发，最近提出了范式转变。治疗应该针对宿主，而不是病毒。这种宿主导向治疗（HDT）策略可以是通过Toll样受体（TLR）激活内源性先天免疫应答。重叠感染疗法是一种宿主导向疗法，已在感染两种完全不同的病毒，乙型肝炎（DNA）和丙型肝炎（RNA）病毒的患者中得到验证。 SIT通过持续存在减毒的非致病性禽类双链（ds）RNA病毒载体发挥感染后干扰，其增强内源性先天（IFN）反应。因此，SIT可以发展成为一种新的“一种药，多种错误”的广谱抗病毒治疗方法的生物平台。

版权所有©Bentham Science Publishers;如有任何疑问，请发送电子邮件至[email protected]。
关键词：

;病毒干扰;抗病毒基因反应; dsRNA病毒;大流行防范;持续性HBV感染;病毒性重叠感染

结论：
    30950360
DOI：
    10.2174 / 1871526519666190405140858