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 the current study we have directly exposed human PBMC from healthy donors to LASV or to its derivative, ML29. We used PBMC profiling previously to show that ML29 elicited less inflammatory gene expression than MOPV [29] , recapitulating similar profiles of ML29 in naïve primates [26] , and in SIVinfected macaques [30] . Human PBMC exposed to virus is a model for the viremic stage of infection in vivo when much of the transcriptome response is due to non-infectious signal transduction by viral particles [31] [24] . PBMC were used here and in other studies [32] [33] [34] rather than cell lines [35] [36] to more closely simulate the situation in vivo in which circulating blood cells are exposed to virus-infected sites. Here we have shown that in vitro PBMC exposure to arenaviruses with different pathogenic potential, LASV and ML29, resulted in differential expression of ISG, apoptotic, NF-kB, and coagulation pathway genes.