PRJNA718880
Transcriptional analysis of infection with early or late isolates from the 2013-2016 West Africa Ebola virus epidemic do not suggest attenuated pathogenicity as a result of genetic variation
The unprecedented 2013-2016 West Africa Ebola virus (EBOV) epidemic caused by the EBOV-Makona isolate and incurred over 28,000 infections and ~11,000 deaths. Early in this epidemic, several mutations in glycoprotein GP and polymerase L emerged and stabilized. In vitro studies of these new EBOV-Makona isolates showed enhanced fitness and viral replication capacity. However, in vivo studies in mice and rhesus macaques did not provide any evidence of enhanced viral fitness or shedding. All isolates carrying or lacking those mutations resulted in severe or lethal disease in mice and macaques, respectively. The recent report of a possible reemergence of EBOV from a persistent infection in a survivor of the epidemic highlights the urgency for understanding the impact of genetic variation on EBOV pathogenesis. However, potential differences in the host responses are uninvestigated. To address this gap in knowledge, we conducted a comparative transcriptional analysis of the host response to lethal infection with EBOV-Mayinga and -Makona isolates using bivariate, longitudinal and regression analysis.