Omicron sub-lineage BA.5 infection results in attenuated pathology in hACE2 transgenic mice
Abstract A recently emerged sub-lineage of Omicron, BA.5, together with BA.4, caused a fifth wave of coronavirus disease (COVID-19) in South Africa and subsequently emerged as a predominant strain globally due to its high transmissibility. The lethality of BA.5 infection has not been studied in an a...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-09-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05263-6 |
| _version_ | 1827708925918576640 |
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| author | Zaigham Abbas Rizvi Jyotsna Dandotiya Srikanth Sadhu Ritika Khatri Janmejay Singh Virendra Singh Neeta Adhikari Kritika Sharma Vinayake Das Amit Kumar Pandey Bhabatosh Das Guruprasad Medigeshi Shalendra Mani Shinjini Bhatnagar Sweety Samal Anil Kumar Pandey Pramod Kumar Garg Amit Awasthi |
| author_facet | Zaigham Abbas Rizvi Jyotsna Dandotiya Srikanth Sadhu Ritika Khatri Janmejay Singh Virendra Singh Neeta Adhikari Kritika Sharma Vinayake Das Amit Kumar Pandey Bhabatosh Das Guruprasad Medigeshi Shalendra Mani Shinjini Bhatnagar Sweety Samal Anil Kumar Pandey Pramod Kumar Garg Amit Awasthi |
| author_sort | Zaigham Abbas Rizvi |
| collection | DOAJ |
| description | Abstract A recently emerged sub-lineage of Omicron, BA.5, together with BA.4, caused a fifth wave of coronavirus disease (COVID-19) in South Africa and subsequently emerged as a predominant strain globally due to its high transmissibility. The lethality of BA.5 infection has not been studied in an acute hACE2 transgenic (hACE2.Tg) mouse model. Here, we investigated tissue-tropism and immuno-pathology induced by BA.5 infection in hACE2.Tg mice. Our data show that intranasal infection of BA.5 in hACE2.Tg mice resulted in attenuated pulmonary infection and pathology with diminished COVID-19-induced clinical and pathological manifestations. BA.5, similar to Omicron (B.1.1.529), infection led to attenuated production of inflammatory cytokines, anti-viral response and effector T cell response as compared to the ancestral strain of SARS-CoV-2, Wuhan-Hu-1. We show that mice recovered from B.1.1.529 infection showed robust protection against BA.5 infection associated with reduced lung viral load and pathology. Together, our data provide insights as to why BA.5 infection escapes previous SARS-CoV-2 exposure induced-T cell immunity but may result in milder immuno-pathology and alleviated chances of re-infectivity in Omicron-recovered individuals. |
| first_indexed | 2024-03-10T17:13:44Z |
| format | Article |
| id | doaj.art-fa2213b252c144c39434f971c7aca2bd |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-10T17:13:44Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-fa2213b252c144c39434f971c7aca2bd2023-11-20T10:36:25ZengNature PortfolioCommunications Biology2399-36422023-09-016111410.1038/s42003-023-05263-6Omicron sub-lineage BA.5 infection results in attenuated pathology in hACE2 transgenic miceZaigham Abbas Rizvi0Jyotsna Dandotiya1Srikanth Sadhu2Ritika Khatri3Janmejay Singh4Virendra Singh5Neeta Adhikari6Kritika Sharma7Vinayake Das8Amit Kumar Pandey9Bhabatosh Das10Guruprasad Medigeshi11Shalendra Mani12Shinjini Bhatnagar13Sweety Samal14Anil Kumar Pandey15Pramod Kumar Garg16Amit Awasthi17Centre for Immuno-biology and Immunotherapy, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon ExpresswayCentre for Immuno-biology and Immunotherapy, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon ExpresswayCentre for Immuno-biology and Immunotherapy, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon ExpresswayCentre for Viral Therapeutics and Vaccines, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon ExpresswayBioassay Laboratory, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon ExpresswayCentre for Immuno-biology and Immunotherapy, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon ExpresswayCentre for Immuno-biology and Immunotherapy, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon ExpresswayCentre for Immuno-biology and Immunotherapy, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon ExpresswayCentre for Immuno-biology and Immunotherapy, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon ExpresswayCentre for Tuberculosis and Bacterial Diseases Research, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon ExpresswayCentre for Microbiome and Anti-Microbial Resistance, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon ExpresswayBioassay Laboratory, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon ExpresswayCentre for Viral Therapeutics and Vaccines, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon ExpresswayCentre for Maternal and Child Health, Translational Health Science and Technology NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon ExpresswayCentre for Viral Therapeutics and Vaccines, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon ExpresswayDepartment of Physiology, ESIC Medical College & HospitalDepartment of Gastroenterology, All India Institute of Medical SciencesCentre for Immuno-biology and Immunotherapy, Translational Health Science and Technology Institute, NCR-Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon ExpresswayAbstract A recently emerged sub-lineage of Omicron, BA.5, together with BA.4, caused a fifth wave of coronavirus disease (COVID-19) in South Africa and subsequently emerged as a predominant strain globally due to its high transmissibility. The lethality of BA.5 infection has not been studied in an acute hACE2 transgenic (hACE2.Tg) mouse model. Here, we investigated tissue-tropism and immuno-pathology induced by BA.5 infection in hACE2.Tg mice. Our data show that intranasal infection of BA.5 in hACE2.Tg mice resulted in attenuated pulmonary infection and pathology with diminished COVID-19-induced clinical and pathological manifestations. BA.5, similar to Omicron (B.1.1.529), infection led to attenuated production of inflammatory cytokines, anti-viral response and effector T cell response as compared to the ancestral strain of SARS-CoV-2, Wuhan-Hu-1. We show that mice recovered from B.1.1.529 infection showed robust protection against BA.5 infection associated with reduced lung viral load and pathology. Together, our data provide insights as to why BA.5 infection escapes previous SARS-CoV-2 exposure induced-T cell immunity but may result in milder immuno-pathology and alleviated chances of re-infectivity in Omicron-recovered individuals.https://doi.org/10.1038/s42003-023-05263-6 |
| spellingShingle | Zaigham Abbas Rizvi Jyotsna Dandotiya Srikanth Sadhu Ritika Khatri Janmejay Singh Virendra Singh Neeta Adhikari Kritika Sharma Vinayake Das Amit Kumar Pandey Bhabatosh Das Guruprasad Medigeshi Shalendra Mani Shinjini Bhatnagar Sweety Samal Anil Kumar Pandey Pramod Kumar Garg Amit Awasthi Omicron sub-lineage BA.5 infection results in attenuated pathology in hACE2 transgenic mice Communications Biology |
| title | Omicron sub-lineage BA.5 infection results in attenuated pathology in hACE2 transgenic mice |
| title_full | Omicron sub-lineage BA.5 infection results in attenuated pathology in hACE2 transgenic mice |
| title_fullStr | Omicron sub-lineage BA.5 infection results in attenuated pathology in hACE2 transgenic mice |
| title_full_unstemmed | Omicron sub-lineage BA.5 infection results in attenuated pathology in hACE2 transgenic mice |
| title_short | Omicron sub-lineage BA.5 infection results in attenuated pathology in hACE2 transgenic mice |
| title_sort | omicron sub lineage ba 5 infection results in attenuated pathology in hace2 transgenic mice |
| url | https://doi.org/10.1038/s42003-023-05263-6 |
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