SARS-CoV-2 Quasispecies Provides an Advantage Mutation Pool for the Epidemic Variants
ABSTRACT The dynamics of quasispecies afford RNA viruses a great fitness on cell tropism and host range. To study the quasispecies features and the intra-host evolution of SARS-CoV-2, we collected nine confirmed patients and sequenced the haplotypes of spike gene using a single-molecule real-time pl...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2021-09-01
|
| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/Spectrum.00261-21 |
| _version_ | 1818941228617564160 |
|---|---|
| author | Fengming Sun Xiuhua Wang Shun Tan Yunjie Dan Yanqiu Lu Juan Zhang Junli Xu Zhaoxia Tan Xiaomei Xiang Yi Zhou Weiwei He Xing Wan Wei Zhang Yaokai Chen Wenting Tan Guohong Deng |
| author_facet | Fengming Sun Xiuhua Wang Shun Tan Yunjie Dan Yanqiu Lu Juan Zhang Junli Xu Zhaoxia Tan Xiaomei Xiang Yi Zhou Weiwei He Xing Wan Wei Zhang Yaokai Chen Wenting Tan Guohong Deng |
| author_sort | Fengming Sun |
| collection | DOAJ |
| description | ABSTRACT The dynamics of quasispecies afford RNA viruses a great fitness on cell tropism and host range. To study the quasispecies features and the intra-host evolution of SARS-CoV-2, we collected nine confirmed patients and sequenced the haplotypes of spike gene using a single-molecule real-time platform. Fourteen samples were extracted from sputum, nasopharyngeal swabs, or stool, which in total produced 283,655 high-quality circular consensus sequences. We observed a stable quasispecies structure that one master mutant (mean abundance ∼0.70), followed by numerous minor mutants (mean abundance ∼1.21 × 10−3). Under high selective pressure, minor mutants may obtain a fitness advantage and become the master ones. The later predominant substitution D614G existed in the minor mutants of more than one early patient. An epidemic variant had a possibility to be independently originated from multiple hosts. The mutant spectrums covered ∼85% amino acid variations of public genomes (GISAID; frequency ≥ 0.1) and likely provided an advantage mutation pool for the current/future epidemic variants. Notably, 32 of 35 collected antibody escape substitutions were preexistent in the early quasispecies. Virus populations in different tissues/organs revealed potentially independent replications. The quasispecies complexity of sputum samples was significantly lower than that of nasopharyngeal swabs (P = 0.02). Evolution analysis revealed that three continuous S2 domains (HR1, CH, and CD) had undergone a positive selection. Cell fusion-related domains may play a crucial role in adapting to the intrahost immune system. Our findings suggested that future epidemiologic investigations and clinical interventions should consider the quasispecies information that has missed by routine single consensus genome. IMPORTANCE RNA virus population in a host does not consist of a consensus single haplotype but rather an ensemble of related sequences termed quasispecies. The dynamics of quasispecies afford SARS-CoV-2 a great ability on genetic fitness during intrahost evolution. The process is likely achieved by changing the genetic characteristics of key functional genes, such as the spike glycoprotein. Previous studies have applied the next-generation sequencing (NGS) technology to evaluate the quasispecies of SARS-CoV-2, and results indicated a low genetic diversity of the spike gene. However, the NGS platform cannot directly obtain the full haplotypes without assembling, and it is also difficult to predict the extremely low-frequency variations. Therefore, we introduced a single-molecule real-time technology to directly obtain the haplotypes of the RNA population and further study the quasispecies features and intrahost evolution of the spike gene. |
| first_indexed | 2024-12-20T06:52:12Z |
| format | Article |
| id | doaj.art-d90491b6a9f34e5bbcd8fdc2cc351a96 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-12-20T06:52:12Z |
| publishDate | 2021-09-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-d90491b6a9f34e5bbcd8fdc2cc351a962022-12-21T19:49:31ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972021-09-019110.1128/Spectrum.00261-21SARS-CoV-2 Quasispecies Provides an Advantage Mutation Pool for the Epidemic VariantsFengming Sun0Xiuhua Wang1Shun Tan2Yunjie Dan3Yanqiu Lu4Juan Zhang5Junli Xu6Zhaoxia Tan7Xiaomei Xiang8Yi Zhou9Weiwei He10Xing Wan11Wei Zhang12Yaokai Chen13Wenting Tan14Guohong Deng15Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing, ChinaDepartment of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing, ChinaDivision of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, ChinaDepartment of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing, ChinaDivision of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, ChinaDepartment of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing, ChinaBeijing Novogene Company Limited, Beijing, ChinaDepartment of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing, ChinaDepartment of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing, ChinaDepartment of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing, ChinaDepartment of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing, ChinaDepartment of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing, ChinaDepartment of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing, ChinaDivision of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, ChinaDepartment of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing, ChinaDepartment of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medial University), Chongqing, ChinaABSTRACT The dynamics of quasispecies afford RNA viruses a great fitness on cell tropism and host range. To study the quasispecies features and the intra-host evolution of SARS-CoV-2, we collected nine confirmed patients and sequenced the haplotypes of spike gene using a single-molecule real-time platform. Fourteen samples were extracted from sputum, nasopharyngeal swabs, or stool, which in total produced 283,655 high-quality circular consensus sequences. We observed a stable quasispecies structure that one master mutant (mean abundance ∼0.70), followed by numerous minor mutants (mean abundance ∼1.21 × 10−3). Under high selective pressure, minor mutants may obtain a fitness advantage and become the master ones. The later predominant substitution D614G existed in the minor mutants of more than one early patient. An epidemic variant had a possibility to be independently originated from multiple hosts. The mutant spectrums covered ∼85% amino acid variations of public genomes (GISAID; frequency ≥ 0.1) and likely provided an advantage mutation pool for the current/future epidemic variants. Notably, 32 of 35 collected antibody escape substitutions were preexistent in the early quasispecies. Virus populations in different tissues/organs revealed potentially independent replications. The quasispecies complexity of sputum samples was significantly lower than that of nasopharyngeal swabs (P = 0.02). Evolution analysis revealed that three continuous S2 domains (HR1, CH, and CD) had undergone a positive selection. Cell fusion-related domains may play a crucial role in adapting to the intrahost immune system. Our findings suggested that future epidemiologic investigations and clinical interventions should consider the quasispecies information that has missed by routine single consensus genome. IMPORTANCE RNA virus population in a host does not consist of a consensus single haplotype but rather an ensemble of related sequences termed quasispecies. The dynamics of quasispecies afford SARS-CoV-2 a great ability on genetic fitness during intrahost evolution. The process is likely achieved by changing the genetic characteristics of key functional genes, such as the spike glycoprotein. Previous studies have applied the next-generation sequencing (NGS) technology to evaluate the quasispecies of SARS-CoV-2, and results indicated a low genetic diversity of the spike gene. However, the NGS platform cannot directly obtain the full haplotypes without assembling, and it is also difficult to predict the extremely low-frequency variations. Therefore, we introduced a single-molecule real-time technology to directly obtain the haplotypes of the RNA population and further study the quasispecies features and intrahost evolution of the spike gene.https://journals.asm.org/doi/10.1128/Spectrum.00261-21quasispeciesSARS-CoV-2COVID-19spike gene |
| spellingShingle | Fengming Sun Xiuhua Wang Shun Tan Yunjie Dan Yanqiu Lu Juan Zhang Junli Xu Zhaoxia Tan Xiaomei Xiang Yi Zhou Weiwei He Xing Wan Wei Zhang Yaokai Chen Wenting Tan Guohong Deng SARS-CoV-2 Quasispecies Provides an Advantage Mutation Pool for the Epidemic Variants Microbiology Spectrum quasispecies SARS-CoV-2 COVID-19 spike gene |
| title | SARS-CoV-2 Quasispecies Provides an Advantage Mutation Pool for the Epidemic Variants |
| title_full | SARS-CoV-2 Quasispecies Provides an Advantage Mutation Pool for the Epidemic Variants |
| title_fullStr | SARS-CoV-2 Quasispecies Provides an Advantage Mutation Pool for the Epidemic Variants |
| title_full_unstemmed | SARS-CoV-2 Quasispecies Provides an Advantage Mutation Pool for the Epidemic Variants |
| title_short | SARS-CoV-2 Quasispecies Provides an Advantage Mutation Pool for the Epidemic Variants |
| title_sort | sars cov 2 quasispecies provides an advantage mutation pool for the epidemic variants |
| topic | quasispecies SARS-CoV-2 COVID-19 spike gene |
| url | https://journals.asm.org/doi/10.1128/Spectrum.00261-21 |
| work_keys_str_mv | AT fengmingsun sarscov2quasispeciesprovidesanadvantagemutationpoolfortheepidemicvariants AT xiuhuawang sarscov2quasispeciesprovidesanadvantagemutationpoolfortheepidemicvariants AT shuntan sarscov2quasispeciesprovidesanadvantagemutationpoolfortheepidemicvariants AT yunjiedan sarscov2quasispeciesprovidesanadvantagemutationpoolfortheepidemicvariants AT yanqiulu sarscov2quasispeciesprovidesanadvantagemutationpoolfortheepidemicvariants AT juanzhang sarscov2quasispeciesprovidesanadvantagemutationpoolfortheepidemicvariants AT junlixu sarscov2quasispeciesprovidesanadvantagemutationpoolfortheepidemicvariants AT zhaoxiatan sarscov2quasispeciesprovidesanadvantagemutationpoolfortheepidemicvariants AT xiaomeixiang sarscov2quasispeciesprovidesanadvantagemutationpoolfortheepidemicvariants AT yizhou sarscov2quasispeciesprovidesanadvantagemutationpoolfortheepidemicvariants AT weiweihe sarscov2quasispeciesprovidesanadvantagemutationpoolfortheepidemicvariants AT xingwan sarscov2quasispeciesprovidesanadvantagemutationpoolfortheepidemicvariants AT weizhang sarscov2quasispeciesprovidesanadvantagemutationpoolfortheepidemicvariants AT yaokaichen sarscov2quasispeciesprovidesanadvantagemutationpoolfortheepidemicvariants AT wentingtan sarscov2quasispeciesprovidesanadvantagemutationpoolfortheepidemicvariants AT guohongdeng sarscov2quasispeciesprovidesanadvantagemutationpoolfortheepidemicvariants |