Means and compositions of matter are disclosed for stimulation of innate immunity in controlling, substantially reducing, and/or clearing filoviral infections including Margburg and Ebola virus. In one embodiment an activator of dendritic cells (DC) is provided to replicate a state similar to one found in patients that significantly overcome filoviral infections. In one particular embodiment the HMGB1-derived peptide SAFFLFCSE or derivatives thereof are administered in a pharmacologically acceptable formulation. Efficacy may be augmented by administration of agents that increase monocyte numbers, which are thereafter stimulating to differentiate along the DC pathway by filoviral infection, or by administration of flt-3 ligand. Alternatively GM-CSF may be administered. Naturally derived compounds such as plant based lectins are also utilized to stimulate DC maturation through activation of receptors such as toll like receptors (TLR).