The immune status of an individual is a major determinant of disease severity in West Nile virus (WNV)-infected patients. In our previous study, we have shown that immunocompetent New Zealand White rabbits (NZWRs) are phenotypically resistant to WNV infection, thus presenting a suitable model for studying immune mechanisms associated with effective virus control [1]. The current study used corticosteroid-treated NZWRs to model immunosuppression. Maximal effects on immunological parameters, such as hematological profile, thymocyte proliferation and blood cell cytokine transcript profile, was observed on day 3 post-treatment. However, contrary to our hypothesis, intradermal WNV infection at this time post-corticosteroid treatment produced significantly lower viremic titer on day 1 post-infection (pi) in treated rabbits, relative to that in the untreated controls. Draining lymph node viral load on days 1, 3, and 7 pi was comparable between the two groups. Despite these results, viral antigen was detected in a broader range of lymphoid tissues in 2/3 of the treated rabbits on day 3 pi, suggesting more widespread viral dissemination without the need for higher viremia and replication in draining lymph node. Preliminary RNAseq performed on the draining lymph node suggested differential gene expression between treated rabbits and uninfected controls. Viral population dynamics is also being examined in order to determine the level of viral genotypic diversity between the groups, and to assess any links of this diversity with the local immune gene expression profile. This study therefore gives an insight into the spectrum of virus control mechanisms in individuals with varying immune status during the acute phase of the infection.