ImiGene, Inc., Rockville, MD, USA
HepC, Inc., Budapest, Hungary
Infect Disord Drug Targets. 2020;20(4):423-432. doi: 10.2174/1871526519666190405140858.
Viral interference, originally, referred to a state of temporary immunity, is a state 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.
病毒干扰，最初是指一种暂时免疫状态，是指感染一种病毒会限制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超过第一种病毒。事实上，两种病毒之间的优势可以交替。感染上皮细胞后，I 型干扰素基因的表达被多次上调。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，因此有人提出，病毒诱导非特异性局部暂时免疫状态可能是控制病毒感染的一种策略。临床观察也支持这一理论，这为超感染疗法（SIT）的发展提供了依据。SIT 是一种创新的治疗方法，使用非致病性病毒感染携带致病性病毒的患者。为了实现持续性病毒感染的功能性治愈和广谱抗病毒药物的开发，最近提出了一种范式转变。治疗方法不应针对病毒，而应针对宿主。这种宿主定向疗法（HDT）策略可以是通过 Toll 样受体（TLRs）激活内源性先天免疫反应。超感染疗法就是这样一种宿主定向疗法，已经在感染两种完全不同病毒（乙型肝炎（DNA）和丙型肝炎（RNA）病毒）的患者中得到了验证。SIT 通过持续存在的减毒非致病性禽双链（ds）RNA 病毒载体发挥感染后干扰作用，从而增强内源性先天（IFN）反应。因此，SIT 可以开发成为一种新的“一种药物，多种病菌”广谱抗病毒治疗方法的生物平台。
