Aspects of porcine immunological response to Nipah virus
Nipah virus (NiV) is a highly pathogenic and zoonotic paramyxovirus in the subfamily Paramyxovirinae, genus Henipavirus. The virus causes outbreaks of severe febrile encephalitis with a high mortality rate in humans, and of encephalitic and respiratory disease but with a low mortality rate in pigs. The innate immune response has a critical role in limiting viral infection by activating antiviral state and adaptive immune response. As pigs are able to overcome the infection with NiV, the working hypothesis was that IFN induced signaling pathways are not completely inhibited by NiV in infected porcine cells enabling an antiviral state to be established. Indeed, there was no block of eIF2α phosphorylation in porcine fibroblast (ST) and monocytic-like (IPAM) cells, and human fibroblast (MRC5) cells. To address the potential activation of an alternative IFN induced pathway, the MAPK signaling pathways were examined. The findings revealed that NiV infection triggers different kinetics of phosphorylation of ERK and p38 MAPK in the selected cell types. The data also indicates that p38 MAPK to be indispensable for NiV replication in vitro especially in immune cells. As the involvement of immune cells in viral spread and in immune modulation of porcine adaptive immune response were reported. The next hypothesis stated that NiV infects immune cells and affects the population frequencies of PBMC in pigs. In vitro, productive viral replication was detected in monocytes, CD6+CD8+ T lymphocytes and NK cells, by recovery of infectious virus, anti-genomic RNA and detection of structural N and non-structural C proteins. B lymphocytes, CD4-CD8-, as well as CD4+CD8- T lymphocytes were not permissive to NiV. In NiV infected piglets, the expansion of the CD4+CD8- T cells early post infection was consistent with a functional humoral response. In contrast, significant drop in CD4+CD8- T cell frequency was observed in piglets which succumbed to the experimental infection, supporting vaccine studies that antibody development is a critical component of protective immune response. Thus, both aspects of innate and adaptive immune response are affected and contribute to NiV pathogenesis. These findings will help researchers to design and establish vaccination programs that would be more effective in pigs.
Stachowiak B, Weingartl HM (2012) Nipah Virus Infects Specific Subsets of Porcine Peripheral Blood Mononuclear Cells. PLoS ONE 7(1): e30855. doi:10.1371/journal.pone.0030855