Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Viruses. 2024 Jul 29;16(8):1215. doi: 10.3390/v16081215.
Adeno-associated viruses (AAVs) are small, non-enveloped viruses that package a single-stranded (ss)DNA genome of 4.7 kilobases (kb) within their T = 1 icosahedral capsid. AAVs are replication-deficient viruses that require a helper virus to complete their life cycle. Recombinant (r)AAVs have been utilized as gene delivery vectors for decades in gene therapy applications. So far, six rAAV-based gene medicines have been approved by the US FDA. The 4.7 kb ssDNA genome of AAV encodes nine proteins, including three viral structural/capsid proteins, VP1, VP2, and VP3; four large nonstructural proteins (replication-related proteins), Rep78/68 and Rep52/40; and two small nonstructural proteins. The two nonstructured proteins are viral accessory proteins, namely the assembly associated protein (AAP) and membrane-associated accessory protein (MAAP). Although the accessory proteins are conserved within AAV serotypes, their functions are largely obscure. In this review, we focus on the expression strategy and functional properties of the small nonstructural proteins of AAVs.
腺相关病毒 (AAV) 是一种小型、无包膜病毒，其 T=1 二十面体衣壳内包装了一条 4.7 千碱基 (kb) 的单链 (ss)DNA 基因组。AAV 是复制缺陷型病毒，需要辅助病毒才能完成其生命周期。重组 (r)AAV 已在基因治疗应用中作为基因传递载体使用了几十年。迄今为止，已有六种基于 rAAV 的基因药物获得美国 FDA 批准。AAV 的 4.7 kb ssDNA 基因组编码九个蛋白，包括三个病毒结构/衣壳蛋白 VP1、VP2 和 VP3；四个大型非结构蛋白（复制相关蛋白）Rep78/68 和 Rep52/40；和两个小非结构蛋白。这两个非结构蛋白是病毒辅助蛋白，即组装相关蛋白 (AAP) 和膜相关辅助蛋白 (MAAP)。尽管辅助蛋白在 AAV 血清型中是保守的，但它们的功能在很大程度上仍是未知的。在这篇综述中，我们重点介绍 AAV 小非结构蛋白的表达策略和功能特性。
