Collins Natalie D, Shan Chao, Nunes Bruno T D, Widen Steven G, Shi Pei-Yong, Barrett Alan D T, Sarathy Vanessa V
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Viral Disease Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Vaccines (Basel). 2020 Apr 3;8(2):161. doi: 10.3390/vaccines8020161.
(ZIKV) is a mosquito-transmitted positive-sense RNA virus in the family . Candidate live-attenuated vaccine (LAV) viruses with engineered deletions in the 3' untranslated region (UTR) provide immunity and protection in animal models of ZIKV infection, and phenotypic studies show that LAVs retain protective abilities following in vitro passage. The present study investigated the genetic diversity of wild-type (WT) parent ZIKV and its candidate LAVs using next generation sequencing analysis of five sequential in vitro passages. The results show that genomic entropy of WT ZIKV steadily increases during in vitro passage, whereas that of LAVs also increased by passage number five but was variable throughout passaging. Additionally, clusters of single nucleotide variants (SNVs) were found to be present in the pre-membrane/membrane (prM), envelope (E), nonstructural protein NS1 (NS1), and other nonstructural protein genes, depending on the specific deletion, whereas in the parent WT ZIKV, they are more abundant in prM and NS1. Ultimately, both the parental WT and LAV derivatives increase in genetic diversity, with evidence of adaptation following passage.
寨卡病毒（ZIKV）是一种由蚊子传播的正链RNA病毒，属于[病毒所属科名未给出]科。在3'非翻译区（UTR）经过基因工程缺失改造的候选减毒活疫苗（LAV）病毒，在寨卡病毒感染的动物模型中可提供免疫和保护作用，并且表型研究表明，减毒活疫苗在体外传代后仍保留保护能力。本研究通过对连续五次体外传代进行下一代测序分析，调查了野生型（WT）亲本寨卡病毒及其候选减毒活疫苗的遗传多样性。结果表明，野生型寨卡病毒的基因组熵在体外传代过程中稳步增加，而减毒活疫苗的基因组熵在传代至第五代时也有所增加，但在整个传代过程中存在变化。此外，根据特定缺失情况，在前膜/膜蛋白（prM）、包膜蛋白（E）、非结构蛋白NS1以及其他非结构蛋白基因中发现了单核苷酸变异（SNV）簇，而在亲本野生型寨卡病毒中，它们在prM和NS1中更为丰富。最终，亲本野生型和减毒活疫苗衍生物的遗传多样性均增加，传代后有适应的证据。
