On both the 7-day ( Figure 4A , C, E, G) and 14-day ( Figure 4B , D, F, H) pretreatments, DEF201 significantly reduced day-7 viral loads and liver disease (ALT) compared to the controls. The absence of elevated ALT levels in the DEF201-treated hamsters may be explained by the 2-3 log 10 reduction in liver virus burden ( Figure 4E , F) and a delay in the development of liver disease. Although tissue titers were slightly lower when DEF201 was given 7 days prior to challenge compared to the 14 day pretreatment, this was not evident with serum viral burden. Because most animals had measurable replicating PICV ( Figure 4C-H) , it is likely that survivors would have been immunized and protected from subsequent challenge. This may not be the case with hamsters treated with DEF201 24 h prior to challenge since most had no detectable virus titers in spleen, liver, or serum on day 7 of PICV infection ( Figure 2B-D) .