Distinct transcriptional responses to fatal Ebola virus infection in cynomolgus and rhesus macaques suggest species-specific immune responses
Ebola virus (EBOV) is a negative single-stranded RNA virus within the Filoviridae family and the causative agent of Ebola virus disease (EVD). Nonhuman primates (NHPs), including cynomolgus and rhesus macaques, are considered the gold standard animal model to interrogate mechanisms of EBOV pathogene...
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| Language: | English |
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Taylor & Francis Group
2021-01-01
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| Series: | Emerging Microbes and Infections |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2021.1942229 |
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| author | Amanda N. Pinski Kevin J. Maroney Andrea Marzi Ilhem Messaoudi |
| author_facet | Amanda N. Pinski Kevin J. Maroney Andrea Marzi Ilhem Messaoudi |
| author_sort | Amanda N. Pinski |
| collection | DOAJ |
| description | Ebola virus (EBOV) is a negative single-stranded RNA virus within the Filoviridae family and the causative agent of Ebola virus disease (EVD). Nonhuman primates (NHPs), including cynomolgus and rhesus macaques, are considered the gold standard animal model to interrogate mechanisms of EBOV pathogenesis. However, despite significant genetic similarity (>90%), NHP species display different clinical presentation following EBOV infection, notably a ∼1–2 days delay in disease progression. Consequently, evaluation of therapeutics is generally conducted in rhesus macaques, whereas cynomolgus macaques are utilized to determine efficacy of preventative treatments, notably vaccines. This observation is in line with reported differences in disease severity and host responses between these two NHP following infection with simian varicella virus, influenza A and SARS-CoV-2. However, the molecular underpinnings of these differential outcomes following viral infections remain poorly defined. In this study, we compared published transcriptional profiles obtained from cynomolgus and rhesus macaques infected with the EBOV-Makona Guinea C07 using bivariate and regression analyses to elucidate differences in host responses. We report the presence of a shared core of differentially expressed genes (DEGs) reflecting EVD pathology, including aberrant inflammation, lymphopenia, and coagulopathy. However, the magnitudes of change differed between the two macaque species. These findings suggest that the differential clinical presentation of EVD in these two species is mediated by altered transcriptional responses. |
| format | Article |
| id | doaj-art-a186107343c246d2a1d6933b00a36298 |
| institution | OA Journals |
| issn | 2222-1751 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj-art-a186107343c246d2a1d6933b00a362982025-08-20T01:49:09ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512021-01-011011320133010.1080/22221751.2021.1942229Distinct transcriptional responses to fatal Ebola virus infection in cynomolgus and rhesus macaques suggest species-specific immune responsesAmanda N. Pinski0Kevin J. Maroney1Andrea Marzi2Ilhem Messaoudi3Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine CA, USADepartment of Molecular Biology and Biochemistry, University of California Irvine, Irvine CA, USALaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH, Rocky Mountain Laboratories, Hamilton, MT, USADepartment of Molecular Biology and Biochemistry, University of California Irvine, Irvine CA, USAEbola virus (EBOV) is a negative single-stranded RNA virus within the Filoviridae family and the causative agent of Ebola virus disease (EVD). Nonhuman primates (NHPs), including cynomolgus and rhesus macaques, are considered the gold standard animal model to interrogate mechanisms of EBOV pathogenesis. However, despite significant genetic similarity (>90%), NHP species display different clinical presentation following EBOV infection, notably a ∼1–2 days delay in disease progression. Consequently, evaluation of therapeutics is generally conducted in rhesus macaques, whereas cynomolgus macaques are utilized to determine efficacy of preventative treatments, notably vaccines. This observation is in line with reported differences in disease severity and host responses between these two NHP following infection with simian varicella virus, influenza A and SARS-CoV-2. However, the molecular underpinnings of these differential outcomes following viral infections remain poorly defined. In this study, we compared published transcriptional profiles obtained from cynomolgus and rhesus macaques infected with the EBOV-Makona Guinea C07 using bivariate and regression analyses to elucidate differences in host responses. We report the presence of a shared core of differentially expressed genes (DEGs) reflecting EVD pathology, including aberrant inflammation, lymphopenia, and coagulopathy. However, the magnitudes of change differed between the two macaque species. These findings suggest that the differential clinical presentation of EVD in these two species is mediated by altered transcriptional responses.https://www.tandfonline.com/doi/10.1080/22221751.2021.1942229EBOVtranscriptomicsnonhuman primateNHPimmunitylongitudinal |
| spellingShingle | Amanda N. Pinski Kevin J. Maroney Andrea Marzi Ilhem Messaoudi Distinct transcriptional responses to fatal Ebola virus infection in cynomolgus and rhesus macaques suggest species-specific immune responses Emerging Microbes and Infections EBOV transcriptomics nonhuman primate NHP immunity longitudinal |
| title | Distinct transcriptional responses to fatal Ebola virus infection in cynomolgus and rhesus macaques suggest species-specific immune responses |
| title_full | Distinct transcriptional responses to fatal Ebola virus infection in cynomolgus and rhesus macaques suggest species-specific immune responses |
| title_fullStr | Distinct transcriptional responses to fatal Ebola virus infection in cynomolgus and rhesus macaques suggest species-specific immune responses |
| title_full_unstemmed | Distinct transcriptional responses to fatal Ebola virus infection in cynomolgus and rhesus macaques suggest species-specific immune responses |
| title_short | Distinct transcriptional responses to fatal Ebola virus infection in cynomolgus and rhesus macaques suggest species-specific immune responses |
| title_sort | distinct transcriptional responses to fatal ebola virus infection in cynomolgus and rhesus macaques suggest species specific immune responses |
| topic | EBOV transcriptomics nonhuman primate NHP immunity longitudinal |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2021.1942229 |
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