Author(s): Collins, Natalie D ; Shan, Chao ; Nunes, Bruno Tardelli Diniz ; Widen, Steven G ; Shi, Pei-Yong ; Barrett, Alan D. T ; Sarathy, Vanessa V
Date: 2020
Origin: Oasisbr
Subject(s): Zika virus / patogenicidade; Infec??o por Zika virus / virologia; Vacinas / an?lise; Varia??o Gen?tica; Sequenciamento Completo do Genoma
This research was funded in part by a Gillson-Longenbaugh Foundation grant to A.D.T.B. P.-Y.S. was supported in part by NIH grants AI142759, AI145617, AI127744, AI136126, and UL1TR001439, and awards from the Kleberg Foundation, John S. Dunn Foundation, Amon G. Carter Foundation, and Gillson-Longenbaugh Foundation.
University of Texas Medical Branch. Department of Microbiology and Immunology. Galveston, TX, USA / Walter Reed Army Institute of Research. Viral Disease Branch. Silver Spring, MD, USA.
University of Texas Medical Branch. Department of Biochemistry and Molecular Biology. Galveston, TX, USA / Chinese Academy of Sciences. Wuhan Institute of Virology. Wuhan, China.
University of Texas Medical Branch. Department of Biochemistry and Molecular Biology. Galveston, TX, USA / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil.
University of Texas Medical Branch. Department of Biochemistry and Molecular Biology. Galveston, TX, USA.
University of Texas Medical Branch. Institute for Human Infections and Immunity. Sealy Institute for Vaccine Sciences. Department of Pathology. Galveston, TX, USA.
University of Texas Medical Branch. Institute for Human Infections and Immunity. Sealy Institute for Vaccine Sciences. Department of Pathology. Galveston, TX, USA.
University of Texas Medical Branch. Department of Biochemistry and Molecular Biology. Galveston, TX, USA.
Abstract: Zika virus (ZIKV) is a mosquito-transmitted positive-sense RNA virus in the family Flaviviridae. 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.
