BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University , Guangzhou, Guangdong, China.
Institute of Medical Microbiology, Jinan University , Guangzhou, Guangdong, China.
J Virol. 2023 Oct 31;97(10):e0101423. doi: 10.1128/jvi.01014-23. Epub 2023 Sep 15.
Adenoviruses are widely used in gene therapy and vaccine delivery. Due to the high prevalence of human adenoviruses (HAdVs), the pre-existing immunity against HAdVs in humans is common, which limits the wide and repetitive use of HAdV vectors. In contrast, the pre-existing immunity against simian adenoviruses (SAdVs) is low in humans. Therefore, we performed epidemiological investigations of SAdVs in simians and found that the SAdV prevalence was as high as 33.9%. The whole-genome sequencing and sequence analysis showed SAdV diversity and possible cross species transmission. One isolate with low level of pre-existing neutralizing antibodies in humans was used to construct replication-deficient SAdV vectors with E4orf6 substitution and E1/E3 deletion. Interestingly, we found that the E3 region plays a critical role in its replication in human cells, but the absence of this region could be compensated for by the E4orf6 from HAdV-5 and the E1 expression intrinsic to HEK293 cells.
腺病毒被广泛应用于基因治疗和疫苗传递。由于人类腺病毒（HAdVs）的高流行率，人类对 HAdVs 的预先存在的免疫是常见的，这限制了 HAdV 载体的广泛和重复使用。相比之下，人类对猴腺病毒（SAdVs）的预先存在的免疫较低。因此，我们对灵长类动物中的 SAdV 进行了流行病学调查，发现 SAdV 的流行率高达 33.9%。全基因组测序和序列分析显示 SAdV 具有多样性，并可能发生跨物种传播。我们使用一个在人类中具有低水平预先存在中和抗体的分离株，构建了具有 E4orf6 替代和 E1/E3 缺失的复制缺陷型 SAdV 载体。有趣的是，我们发现 E3 区域在其在人细胞中的复制中起着关键作用，但该区域的缺失可以通过 HAdV-5 的 E4orf6 和 HEK293 细胞固有的 E1 表达来补偿。
