Cellular Immune Response to Marburg Virus Infection in Cynomolgus Macaques

Abstract

Marburg virus (MARV) causes a severe and usually lethal hemorrhagic disease in humans and non-human primates. Here, 16 cynomolgus macaques were experimentally infected with the Ci67 strain of MARV. Blood and spleen samples were collected at various time points after infection to study the immunological response to MARV. Beginning at day 2 and continuing throughout the course of the infection there was a rise in antigen-presenting cells in both the blood and spleen expressing MARV glycoprotein. Natural killer (NK) cells declined in the blood after infection (from 15% on day 0 to 5% on day 6), but a small increase was seen in the spleen samples. Little or no change in CD4(+) or CD8(+) T cells was observed out to day 6 post-exposure in blood, while there was a continual decline in the percentage of CD8(+) T cells in spleen samples. Circulating B cells (defined as CD20(+)) increased during the course of the infection as did CD4(+) CD8(+) (double-positive) T cells. Intracellular cytokine staining indicated that by day 6 a large population of leukocytes in the spleen were producing IFN-alpha; analysis of surface markers indicated that these cells were plasmacytoid dendritic cells based on their expression of CD123(+), but these cells had decreased expression of class II MHC. IL-6 production was detected late in the infection in CD14(+) spleen cells. These results suggest a robust innate immune response to MARV; however, this response was delayed relative to the infection.