PRJNA407110: A conserved transcriptional response to intranasal Ebola virus exposure in nonhuman primates before onset of fever

Summary: Ebola Virus Disease (EVD), caused by the Ebola virus (EBOV), recently made headlines as it cause a large outbreak in West Africa killing more than 11,000 individuals. One aspect of an outbreak of this scale is understanding disease transmission and differences in the host response to infection. In animal models for disease, particularly non-human primate models of disease, a large infectious dose of 1000PFU through intramuscular injection results if a fairly uniformly lethal disease were the animals die after 6-9 days. However, this is not representative of actual transmission routes of infection as humans tend to have variable exposures through cuts and mucosal surfaces and have variable times to death. To determine if a low dose infection through a mucosal surface results in a different host response to infection, we infected 12 cynomologus macaques with 100PFU of EBOV-Makona (EBOV-Mak). To follow the host response to infection, we utilized RNA-Sequencing and a newly developed NanoString codeset to monitor changes in RNA transcripts. We found that despite different onset of disease and some animals presenting with delayed time to death, there was a highly conserved and predictable host response to infection. When animals were aligned based on onset of fever, the first clinical sign of severe disease, the host response to infection was able to be modeled showing a predictable pattern of gene expression with ISG appearing as early as 4 days before fever onset. Together, this shows that lethal EVD has a uniform and predictable response to infection and that expression of a subst of genes is present before the onset of fever.

Overall Design: Whole blood RNA-Seq of 12 Cynomolgus Macaques infected through 2 routes (intranasal (IN) pipette (6) and IN MAD (6)) with EBOV Makona.