Northern pig-tailed macaques (&lt;i&gt;Macaca leonina&lt;/i&gt;) infected with SARS-CoV-2 show rapid viral clearance and persistent immune response

Song, Tian-Zhang; Zheng, Hong-Yi; Han, Jian; Feng, Xiaoli; Liu, Feng-Liang; Yang, Xiang; Jin, Lin; Luo, Rong-Hua; Tian, Ren‐Rong; Liu, Chao; Li, Minghua; Cai, Hourong; Zheng, Yong‐Tang

doi:10.24272/j.issn.2095-8137.2020.334

Cited by 11 publications

(14 citation statements)

References 16 publications

(20 reference statements)

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“…These limitations can be counteracted by using animal models, although severe disease observed in humans cannot be completely recapitulated. Animals, including monkeys, tree shrews, and ferrets, are permissive to SARS-CoV-2 infection ( Deng et al, 2020 ; Fan et al, 2022 ; Kim et al, 2020 ; Muñoz-Fontela et al, 2020 ; Munster et al, 2020 ; Shan et al, 2020 ; Song et al, 2021 ; Song et al, 2020 ; Xu et al, 2020 ), with various animal models developed to test vaccines ( Gao et al, 2020 ; Wang et al, 2020b ) and understand disease progression and immune responses ( Lee et al, 2021 ; Nelson et al, 2022 ). Rhesus macaques are a commonly used non-human primate model for studies on human respiratory viral diseases ( Skinner et al, 2014 ; Yao et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Single-nucleus transcriptomic profiling of multiple organs in a rhesus macaque model of SARS-CoV-2 infection

Wei-hua

Song

et al. 2022

Zoological Research

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Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes diverse clinical manifestations and tissue injuries in multiple organs. However, cellular and molecular understanding of SARS-CoV-2 infection-associated pathology and immune defense features in different organs remains incomplete. Here, we profiled approximately 77 000 single-nucleus transcriptomes of the lung, liver, kidney, and cerebral cortex in rhesus macaques ( Macaca mulatta ) infected with SARS-CoV-2 and healthy controls. Integrated analysis of the multi-organ dataset suggested that the liver harbored the strongest global transcriptional alterations. We observed prominent impairment in lung epithelial cells, especially in AT2 and ciliated cells, and evident signs of fibrosis in fibroblasts. These lung injury characteristics are similar to those reported in patients with coronavirus disease 2019 (COVID-19). Furthermore, we found suppressed MHC class I/II molecular activity in the lung, inflammatory response in the liver, and activation of the kynurenine pathway, which induced the development of an immunosuppressive microenvironment. Analysis of the kidney dataset highlighted tropism of tubule cells to SARS-CoV-2, and we found membranous nephropathy (an autoimmune disease) caused by podocyte dysregulation. In addition, we identified the pathological states of astrocytes and oligodendrocytes in the cerebral cortex, providing molecular insights into COVID-19-related neurological implications. Overall, our multi-organ single-nucleus transcriptomic survey of SARS-CoV-2-infected rhesus macaques broadens our understanding of disease features and antiviral immune defects caused by SARS-CoV-2 infection, which may facilitate the development of therapeutic interventions for COVID-19.

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Section: Introductionmentioning

confidence: 99%

Single-nucleus transcriptomic profiling of multiple organs in a rhesus macaque model of SARS-CoV-2 infection

Wei-hua

Song

et al. 2022

Zoological Research

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“…Many of these disease features are also relevant to severe COVID-19 disease [49][50][51][52][53][54][72][73][74] . A recent report demonstrated that a related species of pigtail macaques showed an abbreviated period of SARS-CoV-2 viral replication but possibly more severe disease than RhM 75 . Thus, PTM may be a reasonable model for severe disease and used to test novel therapeutics and vaccines to prevent disease.…”

Section: Discussionmentioning

confidence: 99%

The pigtail macaque (Macaca nemestrina) model of COVID-19 reproduces diverse clinical outcomes and reveals new and complex signatures of disease

Melton

Doyle-Meyers

Blair

et al. 2021

Preprint

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The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 disease, has killed over four million people worldwide as of July 2021 with infections rising again due to the emergence of highly transmissible variants. Animal models that faithfully recapitulate human disease are critical for assessing SARS-CoV-2 viral and immune dynamics, for understanding mechanisms of disease, and for testing vaccines and therapeutics. Pigtail macaques (PTM, Macaca nemestrina) demonstrate a rapid and severe disease course when infected with simian immunodeficiency virus (SIV), including the development of severe cardiovascular symptoms that are pertinent to COVID-19 manifestations in humans. We thus proposed this species may likewise exhibit severe COVID-19 disease upon infection with SARS-CoV-2. Here, we extensively studied a cohort of SARS-CoV-2-infected PTM euthanized either 6- or 21-days after respiratory viral challenge. We show that PTM demonstrate largely mild-to-moderate COVID-19 disease. Pulmonary infiltrates were dominated by T cells, including CD4+ T cells that upregulate CD8 and express cytotoxic molecules, as well as virus-targeting T cells that were predominantly CD4+. We also noted increases in inflammatory and coagulation markers in blood, pulmonary pathologic lesions, and the development of neutralizing antibodies. Together, our data demonstrate that SARS-CoV-2 infection of PTM recapitulates important features of COVID-19 and reveals new immune and viral dynamics and thus may serve as a useful animal model for studying pathogenesis and testing vaccines and therapeutics.

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“…PTM are also susceptible to influenza infection and show a strong persistent immune response to infection [83]. A recent report demonstrated that a related species of pigtail macaques (Macaca leonine) showed an abbreviated period of SARS-CoV-2 viral replication but possibly more severe disease than RhM [84]. Thus, PTM may be a reasonable model for severe disease and used to test novel therapeutics and vaccines to prevent disease.…”

Section: Plos Pathogensmentioning

confidence: 99%

The pigtail macaque (Macaca nemestrina) model of COVID-19 reproduces diverse clinical outcomes and reveals new and complex signatures of disease

et al. 2021

View full text Add to dashboard Cite

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 disease, has killed over five million people worldwide as of December 2021 with infections rising again due to the emergence of highly transmissible variants. Animal models that faithfully recapitulate human disease are critical for assessing SARS-CoV-2 viral and immune dynamics, for understanding mechanisms of disease, and for testing vaccines and therapeutics. Pigtail macaques (PTM, Macaca nemestrina) demonstrate a rapid and severe disease course when infected with simian immunodeficiency virus (SIV), including the development of severe cardiovascular symptoms that are pertinent to COVID-19 manifestations in humans. We thus proposed this species may likewise exhibit severe COVID-19 disease upon infection with SARS-CoV-2. Here, we extensively studied a cohort of SARS-CoV-2-infected PTM euthanized either 6- or 21-days after respiratory viral challenge. We show that PTM demonstrate largely mild-to-moderate COVID-19 disease. Pulmonary infiltrates were dominated by T cells, including CD4+ T cells that upregulate CD8 and express cytotoxic molecules, as well as virus-targeting T cells that were predominantly CD4+. We also noted increases in inflammatory and coagulation markers in blood, pulmonary pathologic lesions, and the development of neutralizing antibodies. Together, our data demonstrate that SARS-CoV-2 infection of PTM recapitulates important features of COVID-19 and reveals new immune and viral dynamics and thus may serve as a useful animal model for studying pathogenesis and testing vaccines and therapeutics.

show abstract

Northern pig-tailed macaques (<i>Macaca leonina</i>) infected with SARS-CoV-2 show rapid viral clearance and persistent immune response

Cited by 11 publications

References 16 publications

Single-nucleus transcriptomic profiling of multiple organs in a rhesus macaque model of SARS-CoV-2 infection

Single-nucleus transcriptomic profiling of multiple organs in a rhesus macaque model of SARS-CoV-2 infection

The pigtail macaque (Macaca nemestrina) model of COVID-19 reproduces diverse clinical outcomes and reveals new and complex signatures of disease

The pigtail macaque (Macaca nemestrina) model of COVID-19 reproduces diverse clinical outcomes and reveals new and complex signatures of disease

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