|Diaz-san Segundo, Fayna|
|De Los Santos, Teresa|
Submitted to: American Society for Virology Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 6/2/2009
Publication Date: 7/10/2009
Citation: Diaz-San Segundo, F., Moraes, M.P., De Los Santos, T.B., Koster, M.J., Dias, C., Grubman, M.J. 2009. Examing the mechanisms of interferon-induced protection against foot-and-mouth disease virus in swine. American Society for Virology Meeting. Paper No. W21-5: p. 133. Interpretive Summary:
Technical Abstract: Interferons (IFNs) are the first line of the host innate immune defense against viral infection and natural killer (NK) cells, and dendritic cells (DCs), play a key role in the initiation and regulation of both the innate and adaptive immune response. Previously we demonstrated that type I IFN or a combination of type I and II IFNs delivered by replication-defective human adenovirus (Ad5) vectors can protect swine when challenged 1 day later with foot-and-mouth disease virus (FMDV). Protection correlated with the up-regulation of IFN stimulated genes (ISGs) in peripheral blood mononuclear cells (PBMCs). To gain a more comprehensive understanding of the mechanism of protection induced by IFNs, we inoculated swine with Ad5-vectors containing these genes, challenged 1 day later with FMDV and euthanized animals from each group at -1, 1 and 6 days postchallenge (dpc). Blood, skin, and tissues from the immune system were taken and examined for ISG induction and infiltration by immune cells. All animals in the IFN inoculated groups had delayed and decreased clinical signs of disease and viremia as compared to the controls and one animal in the IFN-alpha treated group did not develop clinical disease by 6 dpc. However, animals from all IFN-inoculated groups showed significant up-regulation of INDO, IP-10 and MIP-3 alpha one day after the treatment (dpi) and 2dpi/1dpc in all analyzed organs. Additionally, skin also showed up-regulation of MCP-1, at the same time points. IP-10, MIP-3 alpha and MCP-1 are chemokines involved in the chemo-attraction of cells of the innate immune system, including NK cells and DCs, to the site of viral replication and their up-regulation coincided with a significant increase in the number of epidermal DCs in the skin, the site of FMDV replication. However, we did not detect infiltration of NK cells in the skin although preliminary data indicates that the levels of NK cells increased in the popliteal lymph node (draining lymph node for FMDV) 1dpc. These data suggest that IP-10, MIP-3 alpha and MCP-1 may play a role in protection conferred by IFNs against FMDV, however, direct correlation between up-regulated genes and DC and NK cell migration requires further investigation.