Cargando…

Using Next Generation Sequencing to Study the Genetic Diversity of Candidate Live Attenuated Zika Vaccines

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 sh...

Descripción completa

Detalles Bibliográficos
Autores principales: Collins, Natalie D., Shan, Chao, Nunes, Bruno T.D., Widen, Steven G., Shi, Pei-Yong, Barrett, Alan D.T., Sarathy, Vanessa V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349499/
https://www.ncbi.nlm.nih.gov/pubmed/32260110
http://dx.doi.org/10.3390/vaccines8020161
_version_ 1783557068803801088
author Collins, Natalie D.
Shan, Chao
Nunes, Bruno T.D.
Widen, Steven G.
Shi, Pei-Yong
Barrett, Alan D.T.
Sarathy, Vanessa V.
author_facet Collins, Natalie D.
Shan, Chao
Nunes, Bruno T.D.
Widen, Steven G.
Shi, Pei-Yong
Barrett, Alan D.T.
Sarathy, Vanessa V.
author_sort Collins, Natalie D.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7349499
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-73494992020-07-14 Using Next Generation Sequencing to Study the Genetic Diversity of Candidate Live Attenuated Zika Vaccines Collins, Natalie D. Shan, Chao Nunes, Bruno T.D. Widen, Steven G. Shi, Pei-Yong Barrett, Alan D.T. Sarathy, Vanessa V. Vaccines (Basel) Communication 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. MDPI 2020-04-03 /pmc/articles/PMC7349499/ /pubmed/32260110 http://dx.doi.org/10.3390/vaccines8020161 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Collins, Natalie D.
Shan, Chao
Nunes, Bruno T.D.
Widen, Steven G.
Shi, Pei-Yong
Barrett, Alan D.T.
Sarathy, Vanessa V.
Using Next Generation Sequencing to Study the Genetic Diversity of Candidate Live Attenuated Zika Vaccines
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 Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349499/
https://www.ncbi.nlm.nih.gov/pubmed/32260110
http://dx.doi.org/10.3390/vaccines8020161
work_keys_str_mv AT collinsnatalied usingnextgenerationsequencingtostudythegeneticdiversityofcandidateliveattenuatedzikavaccines
AT shanchao usingnextgenerationsequencingtostudythegeneticdiversityofcandidateliveattenuatedzikavaccines
AT nunesbrunotd usingnextgenerationsequencingtostudythegeneticdiversityofcandidateliveattenuatedzikavaccines
AT widensteveng usingnextgenerationsequencingtostudythegeneticdiversityofcandidateliveattenuatedzikavaccines
AT shipeiyong usingnextgenerationsequencingtostudythegeneticdiversityofcandidateliveattenuatedzikavaccines
AT barrettalandt usingnextgenerationsequencingtostudythegeneticdiversityofcandidateliveattenuatedzikavaccines
AT sarathyvanessav usingnextgenerationsequencingtostudythegeneticdiversityofcandidateliveattenuatedzikavaccines