Distinct transcriptional responses to fatal Ebola virus infection in cynomolgus and rhesus macaques suggest species-specific immune responses.
Emerg Microbes Infect
; 10(1): 1320-1330, 2021 Dec.
Article
em En
| MEDLINE
| ID: mdl-34112056
ABSTRACT
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 â¼1-2 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Regulação da Expressão Gênica
/
Doença pelo Vírus Ebola
/
Macaca fascicularis
/
Macaca mulatta
/
Doenças dos Macacos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Emerg Microbes Infect
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos