B.1.351 SARS-CoV-2 Variant Exhibits Higher Virulence but Less Viral Shedding than That of the Ancestral Strain in Young Nonhuman Primates
ABSTRACT We investigated the distribution, virulence, and pathogenic characteristics of mutated SARS-CoV-2 to clarify the association between virulence and the viral spreading ability of current and future circulating strains. Chinese rhesus macaques were infected with ancestral SARS-CoV-2 strain GD...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-10-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.02263-22 |
| _version_ | 1797989951073157120 |
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| author | Yu Bai Qian He Jinghuan Yang Shuaiyao Lu Qunying Mao Fan Gao Lianlian Bian Jialu Zhang Chaoqiang An Jianyang Liu Xing Wu Wenhai Yu Zhongfang Wang Xiaozhong Peng Junzhi Wang Zhenglun Liang Miao Xu |
| author_facet | Yu Bai Qian He Jinghuan Yang Shuaiyao Lu Qunying Mao Fan Gao Lianlian Bian Jialu Zhang Chaoqiang An Jianyang Liu Xing Wu Wenhai Yu Zhongfang Wang Xiaozhong Peng Junzhi Wang Zhenglun Liang Miao Xu |
| author_sort | Yu Bai |
| collection | DOAJ |
| description | ABSTRACT We investigated the distribution, virulence, and pathogenic characteristics of mutated SARS-CoV-2 to clarify the association between virulence and the viral spreading ability of current and future circulating strains. Chinese rhesus macaques were infected with ancestral SARS-CoV-2 strain GD108 and Beta variant B.1.351 (B.1.351) and assessed for clinical signs, viral distribution, pathological changes, and pulmonary inflammation. We found that GD108 replicated more efficiently in the upper respiratory tract, whereas B.1.351 replicated more efficiently in the lower respiratory tract and lung tissue, implying a reduced viral shedding and spreading ability of B.1.351 compared with that of GD108. Importantly, B.1.351 caused more severe lung injury and dramatically elevated the level of inflammatory cytokines compared with those observed after infection with GD108. Moreover, both B.1.351 and GD108 induced spike-specific T-cell responses at an early stage of infection, with higher levels of interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) in the B.1.351 group and higher levels of interleukin 17 (IL-17) in the GD108 group, indicating a divergent pattern in the T-cell-mediated inflammatory “cytokine storm.” This study provides a basis for exploring the pathogenesis of SARS-CoV-2 variants of concern (VOCs) and establishes an applicable animal model for evaluating the efficacy and safety of vaccines and drugs. IMPORTANCE One of the priorities of the current SARS-CoV-2 vaccine and drug research strategy is to determine the changes in transmission ability, virulence, and pathogenic characteristics of SARS-CoV-2 variants. In addition, nonhuman primates (NHPs) are suitable animal models for the study of the pathogenic characteristics of SARS-CoV-2 and could contribute to the understanding of pathogenicity and transmission mechanisms. As SARS-CoV-2 variants continually emerge and the viral biological characteristics change frequently, the establishment of NHP infection models for different VOCs is urgently needed. In the study, the virulence and tissue distribution of B.1.351 and GD108 were comprehensively studied in NHPs. We concluded that the B.1.351 strain was more virulent but exhibited less viral shedding than the latter. This study provides a basis for determining the pathogenic characteristics of SARS-CoV-2 and establishes an applicable animal model for evaluating the efficacy and safety of vaccines and drugs. |
| first_indexed | 2024-04-11T08:28:46Z |
| format | Article |
| id | doaj.art-35210fe3e4ce4f649a576f5113c0113b |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-04-11T08:28:46Z |
| publishDate | 2022-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-35210fe3e4ce4f649a576f5113c0113b2022-12-22T04:34:37ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-10-0110510.1128/spectrum.02263-22B.1.351 SARS-CoV-2 Variant Exhibits Higher Virulence but Less Viral Shedding than That of the Ancestral Strain in Young Nonhuman PrimatesYu Bai0Qian He1Jinghuan Yang2Shuaiyao Lu3Qunying Mao4Fan Gao5Lianlian Bian6Jialu Zhang7Chaoqiang An8Jianyang Liu9Xing Wu10Wenhai Yu11Zhongfang Wang12Xiaozhong Peng13Junzhi Wang14Zhenglun Liang15Miao Xu16Division of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, People’s Republic of ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, People’s Republic of ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, People’s Republic of ChinaInstitute of Medical Biology, Chinese Academy of Medicine Sciences & Peking Union Medical College, Kunming People’s Republic of ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, People’s Republic of ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, People’s Republic of ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, People’s Republic of ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, People’s Republic of ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, People’s Republic of ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, People’s Republic of ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, People’s Republic of ChinaInstitute of Medical Biology, Chinese Academy of Medicine Sciences & Peking Union Medical College, Kunming People’s Republic of ChinaGuangzhou Laboratory, Guangzhou, ChinaInstitute of Medical Biology, Chinese Academy of Medicine Sciences & Peking Union Medical College, Kunming People’s Republic of ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, People’s Republic of ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, People’s Republic of ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing, People’s Republic of ChinaABSTRACT We investigated the distribution, virulence, and pathogenic characteristics of mutated SARS-CoV-2 to clarify the association between virulence and the viral spreading ability of current and future circulating strains. Chinese rhesus macaques were infected with ancestral SARS-CoV-2 strain GD108 and Beta variant B.1.351 (B.1.351) and assessed for clinical signs, viral distribution, pathological changes, and pulmonary inflammation. We found that GD108 replicated more efficiently in the upper respiratory tract, whereas B.1.351 replicated more efficiently in the lower respiratory tract and lung tissue, implying a reduced viral shedding and spreading ability of B.1.351 compared with that of GD108. Importantly, B.1.351 caused more severe lung injury and dramatically elevated the level of inflammatory cytokines compared with those observed after infection with GD108. Moreover, both B.1.351 and GD108 induced spike-specific T-cell responses at an early stage of infection, with higher levels of interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) in the B.1.351 group and higher levels of interleukin 17 (IL-17) in the GD108 group, indicating a divergent pattern in the T-cell-mediated inflammatory “cytokine storm.” This study provides a basis for exploring the pathogenesis of SARS-CoV-2 variants of concern (VOCs) and establishes an applicable animal model for evaluating the efficacy and safety of vaccines and drugs. IMPORTANCE One of the priorities of the current SARS-CoV-2 vaccine and drug research strategy is to determine the changes in transmission ability, virulence, and pathogenic characteristics of SARS-CoV-2 variants. In addition, nonhuman primates (NHPs) are suitable animal models for the study of the pathogenic characteristics of SARS-CoV-2 and could contribute to the understanding of pathogenicity and transmission mechanisms. As SARS-CoV-2 variants continually emerge and the viral biological characteristics change frequently, the establishment of NHP infection models for different VOCs is urgently needed. In the study, the virulence and tissue distribution of B.1.351 and GD108 were comprehensively studied in NHPs. We concluded that the B.1.351 strain was more virulent but exhibited less viral shedding than the latter. This study provides a basis for determining the pathogenic characteristics of SARS-CoV-2 and establishes an applicable animal model for evaluating the efficacy and safety of vaccines and drugs.https://journals.asm.org/doi/10.1128/spectrum.02263-22SARS-CoV-2 variantviral distributionvirulenceviral sheddingnonhuman primate |
| spellingShingle | Yu Bai Qian He Jinghuan Yang Shuaiyao Lu Qunying Mao Fan Gao Lianlian Bian Jialu Zhang Chaoqiang An Jianyang Liu Xing Wu Wenhai Yu Zhongfang Wang Xiaozhong Peng Junzhi Wang Zhenglun Liang Miao Xu B.1.351 SARS-CoV-2 Variant Exhibits Higher Virulence but Less Viral Shedding than That of the Ancestral Strain in Young Nonhuman Primates Microbiology Spectrum SARS-CoV-2 variant viral distribution virulence viral shedding nonhuman primate |
| title | B.1.351 SARS-CoV-2 Variant Exhibits Higher Virulence but Less Viral Shedding than That of the Ancestral Strain in Young Nonhuman Primates |
| title_full | B.1.351 SARS-CoV-2 Variant Exhibits Higher Virulence but Less Viral Shedding than That of the Ancestral Strain in Young Nonhuman Primates |
| title_fullStr | B.1.351 SARS-CoV-2 Variant Exhibits Higher Virulence but Less Viral Shedding than That of the Ancestral Strain in Young Nonhuman Primates |
| title_full_unstemmed | B.1.351 SARS-CoV-2 Variant Exhibits Higher Virulence but Less Viral Shedding than That of the Ancestral Strain in Young Nonhuman Primates |
| title_short | B.1.351 SARS-CoV-2 Variant Exhibits Higher Virulence but Less Viral Shedding than That of the Ancestral Strain in Young Nonhuman Primates |
| title_sort | b 1 351 sars cov 2 variant exhibits higher virulence but less viral shedding than that of the ancestral strain in young nonhuman primates |
| topic | SARS-CoV-2 variant viral distribution virulence viral shedding nonhuman primate |
| url | https://journals.asm.org/doi/10.1128/spectrum.02263-22 |
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