Transcriptional analysis of lymphoid tissues from infected nonhuman primates reveals the basis for attenuation and immunogenicity of an Ebola virus encoding a mutant VP35 protein

This study investigated the transcriptional response to a low dose (20,000 PFU) of a mutant VP35 Zaire Ebola virus (VP35m) in cynomologus macaques. VP35 is a critical immune evasion factor for Zaire Ebola virus (EBOV). Our previous study using a high dose of VP35m (500,000 PFU) induced a robust transcriptional response in the whole blood of cynomolgus macques; these animals were protected from later backchallenge with a wild-type EBOV. Here, we conducted a transcriptional analysis of whole blood and lymphoid tissues (axillary lymph node, inguinal lymph node, spleen) in cynomolgus macaques following challenge with VP35m. We show robust induction of innate and adaptive processes. Additionally, transcriptional analysis of spleen tissues collected from one nonsurvivor and two survivors following backchallenge with wild type EBOV (Kikwit) demonstrate a distinct disease signature for survival.