Using Next Generation Sequencing to Study the Genetic Diversity of Candidate Live Attenuated Zika Vaccines
<i>Zika virus</i> (ZIKV) is a mosquito-transmitted positive-sense RNA virus in the family <i>Flaviviridae</i>. Candidate live-attenuated vaccine (LAV) viruses with engineered deletions in the 3’ untranslated region (UTR) provide immunity and protection in animal models of ZIK...
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| Format: | Article |
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MDPI AG
2020-04-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/8/2/161 |
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| author | Natalie D. Collins Chao Shan Bruno T.D. Nunes Steven G. Widen Pei-Yong Shi Alan D.T. Barrett Vanessa V. Sarathy |
| author_facet | Natalie D. Collins Chao Shan Bruno T.D. Nunes Steven G. Widen Pei-Yong Shi Alan D.T. Barrett Vanessa V. Sarathy |
| author_sort | Natalie D. Collins |
| collection | DOAJ |
| description | <i>Zika virus</i> (ZIKV) is a mosquito-transmitted positive-sense RNA virus in the family <i>Flaviviridae</i>. 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. |
| first_indexed | 2024-03-10T20:41:39Z |
| format | Article |
| id | doaj.art-1878b86feb3c4b2abf63415ec6c659d3 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T20:41:39Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-1878b86feb3c4b2abf63415ec6c659d32023-11-19T20:35:40ZengMDPI AGVaccines2076-393X2020-04-018216110.3390/vaccines8020161Using Next Generation Sequencing to Study the Genetic Diversity of Candidate Live Attenuated Zika VaccinesNatalie D. Collins0Chao Shan1Bruno T.D. Nunes2Steven G. Widen3Pei-Yong Shi4Alan D.T. Barrett5Vanessa V. Sarathy6Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Pathology, Sealy Institute for Vaccine Sciences, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Pathology, Sealy Institute for Vaccine Sciences, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA<i>Zika virus</i> (ZIKV) is a mosquito-transmitted positive-sense RNA virus in the family <i>Flaviviridae</i>. 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.https://www.mdpi.com/2076-393X/8/2/161next generation sequencing<i>Zika virus</i>genetic diversitylive-attenuated vaccine |
| spellingShingle | Natalie D. Collins Chao Shan Bruno T.D. Nunes Steven G. Widen Pei-Yong Shi Alan D.T. Barrett Vanessa V. Sarathy Using Next Generation Sequencing to Study the Genetic Diversity of Candidate Live Attenuated Zika Vaccines Vaccines next generation sequencing <i>Zika virus</i> genetic diversity live-attenuated vaccine |
| title | Using Next Generation Sequencing to Study the Genetic Diversity of Candidate Live Attenuated Zika Vaccines |
| title_full | Using Next Generation Sequencing to Study the Genetic Diversity of Candidate Live Attenuated Zika Vaccines |
| title_fullStr | Using Next Generation Sequencing to Study the Genetic Diversity of Candidate Live Attenuated Zika Vaccines |
| title_full_unstemmed | Using Next Generation Sequencing to Study the Genetic Diversity of Candidate Live Attenuated Zika Vaccines |
| title_short | Using Next Generation Sequencing to Study the Genetic Diversity of Candidate Live Attenuated Zika Vaccines |
| title_sort | using next generation sequencing to study the genetic diversity of candidate live attenuated zika vaccines |
| topic | next generation sequencing <i>Zika virus</i> genetic diversity live-attenuated vaccine |
| url | https://www.mdpi.com/2076-393X/8/2/161 |
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