Transcriptome Analysis of Human Peripheral Blood Mononuclear Cells Exposed to Lassa Virus and to the Attenuated Mopeia/Lassa Reassortant 29 (ML29), a Vaccine Candidate

Zapata, Juan Carlos; Carrion, Ricardo; Patterson, Jean L.; Crasta, Oswald; Zhang, Yan; Mani, Sachin; Jett, Marti; Poonia, Bhawna; Djavani, Mahmoud; White, David M.; Lukashevich, Igor S.; Salvato, Maria S.

In summary, exposure of human PBMC to viruses modeled the viremic stage of disease, and revealed clear differences between responses to LASV and the attenuated ML29. It remains to be shown whether the charge difference in LASV and ML29 GP2 proteins accounts for their different transcriptome profiles. ISG and genes involved in apoptotic and NF-kB pathways were among the most LASV-affected genes at 24 h after exposure. LASV and not ML29 also affected genes involved in coagulation pathways, e.g. LASV strongly up-regulates THBD suggesting a connection to the vascular abnormalities in fatal cases of LF. Based on our current knowledge about THBD involvement in pro-coagulant and pro-inflammatory pathways, THBD inhibition could be a promising drug target. Additionally, it is important to further investigate the immune response-related genes to elucidate the protective mechanisms that are undermined during LF pathogenesis. Figure S1 Cluster analysis showed that all samples clustered together by time (4, 8, and 24 hpe), by donor (3 healthy donors) and by treatment (unexposed, LASV-exposed, and ML29-exposed cells). Sample IDs are organized by Time-Donor-Stimulus-Sample number. Red color represents up-regulated genes and green color represents down-regulated genes. (TIF)