State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China.
School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China.
Viruses. 2023 May 18;15(5):1192. doi: 10.3390/v15051192.
Human adenovirus 55 (HAdV-55) has recently caused outbreaks of acute respiratory disease (ARD), posing a significant public threat to civilians and military trainees. Efforts to develop antiviral inhibitors and quantify neutralizing antibodies require an experimental system to rapidly monitor viral infections, which can be achieved through the use of a plasmid that can produce an infectious virus. Here, we used a bacteria-mediated recombination approach to construct a full-length infectious cDNA clone, pAd55-FL, containing the whole genome of HadV-55. Then, the green fluorescent protein expression cassette was assembled into pAd55-FL to replace the E3 region to obtain a recombinant plasmid of pAd55-dE3-EGFP. The rescued recombinant virus rAdv55-dE3-EGFP is genetically stable and replicates similarly to the wild-type virus in cell culture. The virus rAdv55-dE3-EGFP can be used to quantify neutralizing antibody activity in sera samples, producing results in concordance with the cytopathic effect (CPE)-based microneutralization assay. Using an rAdv55-dE3-EGFP infection of A549 cells, we showed that the assay could be used for antiviral screening. Our findings suggest that the rAdv55-dE3-EGFP-based high-throughput assay provides a reliable tool for rapid neutralization testing and antiviral screening for HAdV-55.
人腺病毒 55 型(HAdV-55)最近引起了急性呼吸道疾病(ARD)的爆发,对平民和军事受训人员构成了重大的公共威胁。开发抗病毒抑制剂和定量中和抗体的努力需要一个实验系统来快速监测病毒感染,这可以通过使用能够产生感染性病毒的质粒来实现。在这里,我们使用细菌介导的重组方法构建了全长传染性 cDNA 克隆 pAd55-FL,该克隆包含 HAdV-55 的整个基因组。然后,将绿色荧光蛋白表达盒组装到 pAd55-FL 中以取代 E3 区,从而获得了 pAd55-dE3-EGFP 的重组质粒。拯救的重组病毒 rAdv55-dE3-EGFP 在遗传上是稳定的,并且在细胞培养中与野生型病毒的复制方式相似。病毒 rAdv55-dE3-EGFP 可用于定量血清样品中的中和抗体活性,其结果与基于细胞病变效应(CPE)的微量中和测定法一致。使用 rAdv55-dE3-EGFP 感染 A549 细胞,我们表明该测定可用于抗病毒筛选。我们的研究结果表明,基于 rAdv55-dE3-EGFP 的高通量测定为 HAdV-55 的快速中和试验和抗病毒筛选提供了可靠的工具。