Clinical evaluation of highly pathogenic tick-borne flavivirus infection in the mouse model

The objective of this study was to evaluate the feasibility of using clinical parameters to demonstrate disease progression and differentiate between Omsk hemorrhagic fever virus (OHFV) and Russian spring-summer encephalitis virus (RSSEV) infection in the mouse model. Adult C57BL/6 and balb/c mice were infected with either OHFV or RSSEV by footpad inoculation and their temperature, body weight, clinical signs complete blood count, and blood chemistries were evaluated for up to 15 days post-infection (dpi). Clinical evaluation showed that OHFV infection seriously affects balb/c mice, which had shorter average survival times (ASTs) than other groups. On the contrary, RSSEV infection of C57BL/6 mice was more severe than in balb/c mice. During these studies, the development of fever was not observed and the body weight of OHFV infected balb/c and C57BL/6 mice began to decline sharply starting from day 7 and 8, respectively, which correlated with disease onset. Peak increase of globulin and neutrophils was demonstrated after 9 dpi in OHFV infected mice; however, the lymphocyte number was not affected. Viremia was undetectable in these animals with either virus infection, but virus was found in most organs tested. These results indicate marked differences in the clinical signs, pathology, and immune response of mice infected with either OHFV or RSSEV and further validate the use of this mouse model system to evaluate human disease. J. Med. Virol. 81:1261–1269, 2009. © 2009 Wiley-Liss, Inc.