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 comparison to the strong up-regulation by LASV, ML29 has muted expression of INHBA (a negative regulator of IFN-c), IFI44, TNFSF10 (TRAIL), SPP1, and LY6E (RIG-E) genes in the interferon pathway, as well as other genes related to immune response such as integrin alpha-M/beta-2 (ITGAM). These genes were down-regulated at 4, 8 and, some, 24 hpe, suggesting a mechanism to avoid recognition by the innate immune system, and to interfere with essential signals in the pathway that leads to the development of type I immunity [73] , [74] , [75] . For example, interferon-alpha/beta inducible IFI44 is involved in the antiviral action of type I interferon [76] , [77] . ML29 down-regulation of IFI44 probably allows the virus to replicate early during the infection so that a strong immune response can control viral replication and spreading. In support of this notion, other antiviral genes such as RSAD2 (Viperin), and TRIM5 [78] , [79] , [80] were more expressed in LASV than in ML29-exposed PBMC.