University Hospital Essen, University of Duisburg-Essen, Institute for Virology, Essen, Germany.
University Hospital Essen, University of Duisburg-Essen, Institute for Translational HIV Research, Essen, Germany.
mBio. 2023 Dec 19;14(6):e0235723. doi: 10.1128/mbio.02357-23. Epub 2023 Oct 24.
The potency of interferon (IFN)α to restrict viruses was already discovered in 1957. However, until today, only IFNα2 out of the 12 distinct human IFNα subtypes has been therapeutically used against chronic viral infections. There is convincing evidence that other IFNα subtypes are far more efficient than IFNα2 against many viruses. In order to identify critical antiviral residues within the IFNα subtype sequence, we designed hybrid molecules based on the IFNα2 backbone with individual sequence motifs from the more potent subtypes IFNα6 and IFNα14. In different antiviral assays with HIV or HBV, residues binding to IFNAR1 as well as combinations of residues in the IFNAR1 binding region, the putative tunable anchor, and residues outside these regions were identified to be crucial for the antiviral activity of IFNα. Thus, we designed artificial IFNα molecules, based on the clinically approved IFNα2 backbone, but with highly improved antiviral activity against several viruses.
干扰素 (IFN)α 抑制病毒的效力早在 1957 年就已被发现。然而，直到今天，在用于治疗慢性病毒感染的 12 种不同的人源 IFNα 亚型中，只有 IFNα2 被应用于临床。有令人信服的证据表明，在针对许多病毒时，其他 IFNα 亚型比 IFNα2 更有效。为了确定 IFNα 亚型序列中的关键抗病毒残基，我们设计了基于 IFNα2 骨架的杂交分子，其中包含来自更有效的 IFNα6 和 IFNα14 亚型的单个序列基序。在针对 HIV 或 HBV 的不同抗病毒测定中，与 IFNAR1 结合的残基以及 IFNAR1 结合区域、假定的可调锚定以及这些区域之外的残基的组合被确定为 IFNα 抗病毒活性的关键。因此，我们设计了基于临床批准的 IFNα2 骨架的人工 IFNα 分子，但对几种病毒具有更高的抗病毒活性。
