Figure 1.
Mouse survival after infection.
Percent survival of mice (n = 100) infected SC or by aerosol with 1600 PFU of RVFV.
Figure 2.
Mouse daily weight and temperature.
Percent change in baseline of (A) weights and (B) temperature of mice exposed to RVFV SC or by aerosol (N = 5–100/day PI). The symbols represent the mean value and the error bars represent mean standard deviation. Asterisk (*) indicates significantly different values when comparing SC vs. aerosol exposed mice. Single cross (†) indicates significantly different values for SC exposed mice compared to day −1 uninfected controls. Double cross (‡) indicate significantly different values for aerosol exposed mice compared to day −1 uninfected controls.
Figure 3.
Liver enzyme and hematology results.
Analysis of the (A) alanine aminotransferase (ALT), (B) alkaline phosphatase (ALP), (C) percent lymphocytes, and (D) percent neutrophils in RVFV infected mice (N = 4/day PI). The symbols represent the mean concentration and the error bars represent mean standard deviation. Asterisk (*) indicates significantly different values when comparing SC vs. aerosol exposed mice. Single cross (†) indicates significantly different values for SC exposed mice compared to day −1 uninfected controls. Double cross (‡) indicate significantly different values for aerosol exposed mice compared to day −1 uninfected controls.
Figure 4.
Viral titers in (A) plasma, (B) liver, (C) lung, and (D) brain of RVFV infected mice (N = 4/day PI). Error bars represent mean standard deviation. Asterisk (*) indicates significantly different values when comparing SC vs. aerosol exposed mice.
Figure 5.
Lung and liver immunohistochemical findings.
Immunohistochemical findings in the (A–B) lung and (C–D) liver of RVFV infected mice. Minimal viral antigen is detected in the lungs of (A) SC exposed (20×) and (B) aerosol exposed (20×) mice on day 2 PI. Significant viral antigen was detected on day 4 PI in the liver of mice exposed (C) SC (40×) and (D) by aerosol exposure (40×).
Table 1.
Assessment of viral antigen in tissues by immunohistochemistry.
Figure 6.
Nasal turbinate immunohistochemical findings.
Immunohistochemical findings in the nasal turbinates of mice exposed SC (A, C; left side) or by aerosol exposure (B, D; right side). (A) Immunonegative olfactory neuroepithelium and fila olfactoria on day 4 PI in a SC exposed mouse, 40×. (B) Immunoreactive olfactory neuroepithelium and fila olfactoria on day 4 PI in an aerosol exposed mouse, 40×. (C) Rare, focal immunoreactivity of olfactory neuroepithelium and fila olfactoria on day 7 PI in a SC exposed mouse, 40×. (D) In comparison to SC exposed mice, significantly more viral antigen was detected in the olfactory neuroepithelium and fila olfactoria on day 7 PI in aerosol exposed mice, 40×.
Figure 7.
Olfactory bulb immunohistochemical findings.
Immunohistochemical findings in the olfactory bulb of mice exposed SC (A, C, E; left side) or by aerosol exposure (B, D, F; right side). (A) Immunonegative cells of the glomerular layer on day 4 PI in a SC exposed mouse, 40×. (B) Immunoreactive cells of the glomerular layer on day 4 PI in an aerosol exposed mouse, 40×. (C) Immunonegative cells of the olfactory bulb (inset depicts the glomerular layer, 40×) on day 7 PI in a SC exposed mouse, 2×. (D) Strongly immunoreactive olfactory neural cells (inset depicts immunoreactive neurons of the glomerular layer, 40×) on day 7 PI in an aerosol exposed mouse, 2×. (E) Moderate amounts of viral antigen in the glomerular layer on day 8 PI in a SC exposed mouse, 40×. (F). Intensely immunoreactive cells in the glomerular layer on day 8 PI in an aerosol exposed mouse, 40×.
Figure 8.
Brain immunohistochemical findings.
Immunohistochemical findings in the brain of mice exposed SC (A, C; left side) or by aerosol exposure (B, D; right side). (A) Immunonegative brainstem on day 7 PI in a SC exposed mouse, 40×. (B) Immunoreactive neurons in the brainstem on day 7 PI in an aerosol exposed mouse, 40×. (C) Immunoreactive hippocampus, brainstem, and cerebral areas (inset depicts immunoreactive hippocampal neurons, 40×) on day 8 PI in a SC exposed mouse, 2×. (D) Intensely immunoreactive hippocampus, brainstem, and cerebral areas (inset depicts strongly immunoreactive hippocampal neurons, 40×) on day 8 PI in an aerosol exposed mouse, 2×.
Figure 9.
Mouse survival following ribavirin treatment.
Percent survival of mice treated with PBS or ribavirin and infected SC or by aerosol with RVFV (n = 10/group).
Figure 10.
Mouse daily weight and temperature following ribavirin treatment.
Percent change in baseline of (A) weights and (B) temperature of mice treated with PBS or ribavirin and exposed to RVFV SC or by aerosol (N = 10/group). Each symbol indicates the mean and the error bars represent mean standard deviation.
Figure 11.
Viral titers in ribavirin treated mice.
Viral titers in the plasma and tissues of ribavirin treated mice infected by (A) SC exposure or (B) aerosol exposure (N = 4/day PI). Error bars represent mean standard deviation.
Table 2.
The percentage of mice with viral antigen detected in tissues by immunohistochemistry.
Table 3.
Evaluation of the CNS pathology in ribavirin treated and untreated mice on day 8 PI.