State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Virus Res. 2019 Sep;270:197662. doi: 10.1016/j.virusres.2019.197662. Epub 2019 Jul 10.
Human adenovirus type 4 (HAdV4) is an etiological agent of acute respiratory disease (ARD) in pediatric and adult patients. HAdV4 strains can be divided into two major genomic clusters, namely prototype (p)-like viruses and a-like viruses. Here, the complete genome sequence of HAdV4 strain GZ01, isolated from a child with ARD in southern China, is first reported and analyzed. This strain was determined to be of the 4a1 genome-type based on in silico restriction profiles. Then, a replication-competent rAd4DsRed virus, containing the HAdV4 GZ01 infectious genome and expressing the reporter molecule DsRed, was generated and characterized. Recombinant rAd4DsRed can infect AD293, hamster, and mouse cells in which DsRed protein was expressed. No changes in antigenicity and genome replication were detected for rAd4DsRed and wild-type HAdV4. Mice immunized with rAd4DsRed was elicited a marked antibody response to DsRed. A rapid method of testing neutralizing antibodies against HAdV3 and HAdV4 was also established using a mixture of rAd4DsRed and rAd3EGFP. Our results provide the foundation to develop HAdV4 vaccines, potential vector platforms for vaccine and gene therapy, and rapid methods for serological and antiviral screening.
人腺病毒 4 型（HAdV4）是儿科和成年患者急性呼吸道疾病（ARD）的病因。HAdV4 株可分为两个主要基因组群，即原型（p）样病毒和 a 样病毒。本文首次报道并分析了从中国南方一名 ARD 患儿中分离到的 HAdV4 株 GZ01 的全基因组序列。该株基于计算机模拟的限制图谱被确定为 4a1 基因组型。然后，生成并表征了含有 HAdV4 GZ01 感染性基因组并表达报告分子 DsRed 的复制型 rAd4DsRed 病毒。重组 rAd4DsRed 可感染 AD293、仓鼠和表达 DsRed 蛋白的小鼠细胞。rAd4DsRed 和野生型 HAdV4 的抗原性和基因组复制均未发生变化。用 rAd4DsRed 免疫的小鼠对 DsRed 产生了明显的抗体反应。还建立了一种使用 rAd4DsRed 和 rAd3EGFP 混合物检测针对 HAdV3 和 HAdV4 的中和抗体的快速方法。我们的研究结果为开发 HAdV4 疫苗、疫苗和基因治疗的潜在载体平台以及血清学和抗病毒筛选的快速方法提供了基础。
