Host- and Species-Dependent Quasispecies Divergence of Severe Acute Respiratory Syndrome Coronavirus-2 in Non-human Primate Models

Recently, newly emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been continuously reported worldwide. However, the precise evaluation of SARS-CoV-2 microevolution in host is very limited because the exact genetic information of infected virus could not be acqui...

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Main Authors: Eun-Ha Hwang, Hoyin Chung, Green Kim, Hanseul Oh, You Jung An, Philyong Kang, Choong-min Ryu, Jong-Hwan Park, Jungjoo Hong, Bon-Sang Koo
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-07-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2021.694897/full
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author Eun-Ha Hwang
Eun-Ha Hwang
Hoyin Chung
Hoyin Chung
Green Kim
Green Kim
Hanseul Oh
You Jung An
Philyong Kang
Choong-min Ryu
Jong-Hwan Park
Jungjoo Hong
Bon-Sang Koo
author_facet Eun-Ha Hwang
Eun-Ha Hwang
Hoyin Chung
Hoyin Chung
Green Kim
Green Kim
Hanseul Oh
You Jung An
Philyong Kang
Choong-min Ryu
Jong-Hwan Park
Jungjoo Hong
Bon-Sang Koo
author_sort Eun-Ha Hwang
collection DOAJ
description Recently, newly emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been continuously reported worldwide. However, the precise evaluation of SARS-CoV-2 microevolution in host is very limited because the exact genetic information of infected virus could not be acquired in human researches. In this report, we performed deep sequencing for seed virus and SARS-CoV-2 isolated in eight cynomolgus and rhesus macaques at 3 days postinoculation and evaluated single-nucleotide polymorphisms (SNPs) in SARS-CoV-2 by variant analysis. A total of 69 single-nucleotide variants (SNVs) were present in the 5′-untranslated region (UTR), 3′-UTR, ORF1ab, S, ORF3a, ORF8, and N genes of the seed virus passaged in VERO cells. Between those present on the seed virus and those on each SARS-CoV-2 isolated from the lungs of the macaques, a total of 29 variants was identified in 4 coding proteins (ORF1ab, S, ORF3a, and N) and non-coding regions (5′- and 3′-UTR). Variant number was significantly different according to individuals and ranged from 2 to 11. Moreover, the average major frequency variation was identified in six sites between the cynomolgus monkeys and rhesus macaques. As with diverse SNPs in SARS-CoV-2, the values of viral titers in lungs were significantly different according to individuals and species. Our study first revealed that the genomes of SARS-CoV-2 differ according to individuals and species despite infection of the identical virus in non-human primates (NHPs). These results are important for the interpretation of longitudinal studies evaluating the evolution of the SARS-CoV-2 in human beings and development of new diagnostics, vaccine, and therapeutics targeting SARS-CoV-2.
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spelling doaj.art-d150b23f72d443f4b8b1f55bf8b740802022-12-21T19:14:13ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-07-011210.3389/fmicb.2021.694897694897Host- and Species-Dependent Quasispecies Divergence of Severe Acute Respiratory Syndrome Coronavirus-2 in Non-human Primate ModelsEun-Ha Hwang0Eun-Ha Hwang1Hoyin Chung2Hoyin Chung3Green Kim4Green Kim5Hanseul Oh6You Jung An7Philyong Kang8Choong-min Ryu9Jong-Hwan Park10Jungjoo Hong11Bon-Sang Koo12National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, South KoreaLaboratory of Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, South KoreaNational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, South KoreaDepartment of Microbiology, College of Natural Sciences, Chungbuk National University, Cheongju, South KoreaNational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, South KoreaLaboratory of Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, South KoreaNational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, South KoreaNational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, South KoreaFuturistic Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, South KoreaInfectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South KoreaLaboratory of Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, South KoreaNational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, South KoreaNational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, South KoreaRecently, newly emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been continuously reported worldwide. However, the precise evaluation of SARS-CoV-2 microevolution in host is very limited because the exact genetic information of infected virus could not be acquired in human researches. In this report, we performed deep sequencing for seed virus and SARS-CoV-2 isolated in eight cynomolgus and rhesus macaques at 3 days postinoculation and evaluated single-nucleotide polymorphisms (SNPs) in SARS-CoV-2 by variant analysis. A total of 69 single-nucleotide variants (SNVs) were present in the 5′-untranslated region (UTR), 3′-UTR, ORF1ab, S, ORF3a, ORF8, and N genes of the seed virus passaged in VERO cells. Between those present on the seed virus and those on each SARS-CoV-2 isolated from the lungs of the macaques, a total of 29 variants was identified in 4 coding proteins (ORF1ab, S, ORF3a, and N) and non-coding regions (5′- and 3′-UTR). Variant number was significantly different according to individuals and ranged from 2 to 11. Moreover, the average major frequency variation was identified in six sites between the cynomolgus monkeys and rhesus macaques. As with diverse SNPs in SARS-CoV-2, the values of viral titers in lungs were significantly different according to individuals and species. Our study first revealed that the genomes of SARS-CoV-2 differ according to individuals and species despite infection of the identical virus in non-human primates (NHPs). These results are important for the interpretation of longitudinal studies evaluating the evolution of the SARS-CoV-2 in human beings and development of new diagnostics, vaccine, and therapeutics targeting SARS-CoV-2.https://www.frontiersin.org/articles/10.3389/fmicb.2021.694897/fullSARS-CoV-2non-human primatesingle nucleotide variantgenetic variantssingle nucleotide polymorphism
spellingShingle Eun-Ha Hwang
Eun-Ha Hwang
Hoyin Chung
Hoyin Chung
Green Kim
Green Kim
Hanseul Oh
You Jung An
Philyong Kang
Choong-min Ryu
Jong-Hwan Park
Jungjoo Hong
Bon-Sang Koo
Host- and Species-Dependent Quasispecies Divergence of Severe Acute Respiratory Syndrome Coronavirus-2 in Non-human Primate Models
Frontiers in Microbiology
SARS-CoV-2
non-human primate
single nucleotide variant
genetic variants
single nucleotide polymorphism
title Host- and Species-Dependent Quasispecies Divergence of Severe Acute Respiratory Syndrome Coronavirus-2 in Non-human Primate Models
title_full Host- and Species-Dependent Quasispecies Divergence of Severe Acute Respiratory Syndrome Coronavirus-2 in Non-human Primate Models
title_fullStr Host- and Species-Dependent Quasispecies Divergence of Severe Acute Respiratory Syndrome Coronavirus-2 in Non-human Primate Models
title_full_unstemmed Host- and Species-Dependent Quasispecies Divergence of Severe Acute Respiratory Syndrome Coronavirus-2 in Non-human Primate Models
title_short Host- and Species-Dependent Quasispecies Divergence of Severe Acute Respiratory Syndrome Coronavirus-2 in Non-human Primate Models
title_sort host and species dependent quasispecies divergence of severe acute respiratory syndrome coronavirus 2 in non human primate models
topic SARS-CoV-2
non-human primate
single nucleotide variant
genetic variants
single nucleotide polymorphism
url https://www.frontiersin.org/articles/10.3389/fmicb.2021.694897/full
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