For the following experiments, to investigate the effect of mAb D665 on the persistent viral infection, we applied 100 mg at day 14 and 21 post infection, and analyzed the brains at 28 dpi (Fig. 2 B ). Under these conditions the total number of lymphocytes increased significantly after D665 treatment in spleen and LN, but not in the brain (Fig. 2 C) . Furthermore, the proportion of Foxp3 + Tregs increased significantly (approximately 2-fold, P,0.01) in spleen in LN (Fig. 2 D) . Interestingly, histological analyzes revealed that the extent of the viral infection increased considerably after D665 treatment. Large clusters and groups of bright GFP-positive (directly reflecting virus replication) infected neurons emerged in the brains of these mice (Fig. 3 A) . This was in striking contrast to the brains of untreated mice at 28 dpi, which contain only a limited number of infected neurons (Fig. 3 B) . It is also strikingly different from brains at 14 dpi, when the treatment with D665 begins. At this time point areas with weak (vanishing) GFP expression are observed, that represent areas from which virus is being eliminated (Fig. 3 C) . The quantification demonstrated approximately 100-fold more infected cells per brain in D665treated animals in comparison to control animals at 28 dpi ( Fig. 3 D, compare lanes 3 and 5; differences were highly significant: P,0.0001). Two weeks later, at 42 dpi, the number of infected cells was reduced, but still higher than in control animals ( 