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Eastern equine encephalitis virus in mice I: clinical course and outcome are dependent on route of exposure.

Honnold SP, Mossel EC, Bakken RR, Fisher D, Lind CM, Cohen JW, Eccleston LT, Spurgers KB, Erwin-Cohen R, Bradfute SB, Maheshwari RK, Glass PJ - Virol. J. (2015)

Bottom Line: The majority of those animals exposed by the aerosol route developed severe clinical signs by 4 dpi.Significant differences were also observed in the viral titers of target tissues, with virus being detected in the brain at 6 hpi in the aerosol study.Aerosol exposure to EEEV results in acute onset of clinical signs, rapid neuroinvasion, and 100 % mortality.

View Article: PubMed Central - PubMed

Affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, 21702, USA. shelley.p.honnold.mil@mail.mil.

ABSTRACT

Background: Eastern equine encephalitis virus (EEEV), an arbovirus, is an important human and veterinary pathogen belonging to one of seven antigenic complexes in the genus Alphavirus, family Togaviridae. EEEV is considered the most deadly of the mosquito-borne alphaviruses due to the high case fatality rate associated with clinical infections, reaching up to 75 % in humans and 90 % in horses. In patients that survive acute infection, neurologic sequelae are often devastating. Although natural infections are acquired by mosquito bite, EEEV is also highly infectious by aerosol. This fact, along with the relative ease of production and stability of this virus, has led it to being identified as a potential agent of bioterrorism.

Methods: To characterize the clinical course and outcome of EEEV strain FL93-939 infection, we compared clinical parameters, cytokine expression, viremia, and viral titers in numerous tissues of mice exposed by various routes. Twelve-week-old female BALB/c mice were infected by the intranasal, aerosol, or subcutaneous route. Mice were monitored for clinical signs of disease and euthanized at specified time points (6 hpi through 8 dpi). Blood and tissues were harvested for cytokine analysis and/or viral titer determination.

Results: Although all groups of animals exhibited similar clinical signs after inoculation, the onset and severity differed. The majority of those animals exposed by the aerosol route developed severe clinical signs by 4 dpi. Significant differences were also observed in the viral titers of target tissues, with virus being detected in the brain at 6 hpi in the aerosol study.

Conclusion: The clinical course and outcome of EEEV infection in mice is dependent on route of exposure. Aerosol exposure to EEEV results in acute onset of clinical signs, rapid neuroinvasion, and 100 % mortality.

No MeSH data available.


Related in: MedlinePlus

Complete blood counts in mice exposed to EEEV strain FL93-939 either by the aerosol or subcutaneous routes. Numbers shown are the mean ± standard deviation of total white blood cells (a), lymphocytes (b), neutrophils (c), monocytes (d), platelets (e), and red blood cells (f), at each time point (n = 10 per time point per route). Normal ranges (black boxes) were determined from control animals (n = 20) combined from both routes of exposure (white blood cells = 2.4-6.3 x 103/μL, neutrophils = 0.5-1.8 x 103/μL, lymphocytes = 1.2-4.6 x 103/μL, monocytes = 0.1-0.3 x 103/μL, red blood cells = 7.6-8.7 x 106/μL, and platelets = 458.9-914.6 x 103/μL). Note that the aerosol study was terminated at 4 dpi because 90 % of the animals in the 5dpi group were showing moderate to severe signs of clinical disease
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Fig3: Complete blood counts in mice exposed to EEEV strain FL93-939 either by the aerosol or subcutaneous routes. Numbers shown are the mean ± standard deviation of total white blood cells (a), lymphocytes (b), neutrophils (c), monocytes (d), platelets (e), and red blood cells (f), at each time point (n = 10 per time point per route). Normal ranges (black boxes) were determined from control animals (n = 20) combined from both routes of exposure (white blood cells = 2.4-6.3 x 103/μL, neutrophils = 0.5-1.8 x 103/μL, lymphocytes = 1.2-4.6 x 103/μL, monocytes = 0.1-0.3 x 103/μL, red blood cells = 7.6-8.7 x 106/μL, and platelets = 458.9-914.6 x 103/μL). Note that the aerosol study was terminated at 4 dpi because 90 % of the animals in the 5dpi group were showing moderate to severe signs of clinical disease

Mentions: When an adequate volume of blood was collected at euthanasia, a complete blood count was performed on individual animals from the AE and SC studies. Group mean results are shown in Fig. 3. Significant variation among individuals was observed, which resulted in large standard deviations in some groups. However, in AE infected animals, there was a general decrease in the total number of white blood cells (WBC) (leukopenia) by 2 dpi, with the group mean value dropping below the normal (control group) range and remaining low through the end of the study. This decrease in WBCs was characterized by a decrease in lymphocytes (lymphopenia), while the number of neutrophils and monocytes (Fig. 3a-d), as well as the number of eosinophils and basophils (data not shown), remained within the normal range. Significant differences (p < 0.05) were observed in total WBC and number of lymphocytes between infected and uninfected animals from 12 hpi through the end of the study (Table 2). Interestingly, while the mean total number of neutrophils in infected animals never fell below the normal range at any time point, there were significant differences in the total number of neutrophils present in infected and uninfected animals at every time point. There were also significant differences in the number of platelets at 0.25 dpi and 0.5 dpi hpi. A leukopenia was also observed in SC infected animals; however, this occurred earlier, at 1 dpi, and when evaluating group means, was characterized by both a lymphopenia as well as a neutropenia. These values remained low through 2 dpi for lymphocytes and 3 dpi for neutrophils, after which time all mean values returned to the normal range for the remainder of the study. No significant differences between SC infected and uninfected animals were observed at any of the time points. The AE and SC group mean values for red blood cells remained within the normal range for the duration of the study.Fig. 3


Eastern equine encephalitis virus in mice I: clinical course and outcome are dependent on route of exposure.

Honnold SP, Mossel EC, Bakken RR, Fisher D, Lind CM, Cohen JW, Eccleston LT, Spurgers KB, Erwin-Cohen R, Bradfute SB, Maheshwari RK, Glass PJ - Virol. J. (2015)

Complete blood counts in mice exposed to EEEV strain FL93-939 either by the aerosol or subcutaneous routes. Numbers shown are the mean ± standard deviation of total white blood cells (a), lymphocytes (b), neutrophils (c), monocytes (d), platelets (e), and red blood cells (f), at each time point (n = 10 per time point per route). Normal ranges (black boxes) were determined from control animals (n = 20) combined from both routes of exposure (white blood cells = 2.4-6.3 x 103/μL, neutrophils = 0.5-1.8 x 103/μL, lymphocytes = 1.2-4.6 x 103/μL, monocytes = 0.1-0.3 x 103/μL, red blood cells = 7.6-8.7 x 106/μL, and platelets = 458.9-914.6 x 103/μL). Note that the aerosol study was terminated at 4 dpi because 90 % of the animals in the 5dpi group were showing moderate to severe signs of clinical disease
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4588493&req=5

Fig3: Complete blood counts in mice exposed to EEEV strain FL93-939 either by the aerosol or subcutaneous routes. Numbers shown are the mean ± standard deviation of total white blood cells (a), lymphocytes (b), neutrophils (c), monocytes (d), platelets (e), and red blood cells (f), at each time point (n = 10 per time point per route). Normal ranges (black boxes) were determined from control animals (n = 20) combined from both routes of exposure (white blood cells = 2.4-6.3 x 103/μL, neutrophils = 0.5-1.8 x 103/μL, lymphocytes = 1.2-4.6 x 103/μL, monocytes = 0.1-0.3 x 103/μL, red blood cells = 7.6-8.7 x 106/μL, and platelets = 458.9-914.6 x 103/μL). Note that the aerosol study was terminated at 4 dpi because 90 % of the animals in the 5dpi group were showing moderate to severe signs of clinical disease
Mentions: When an adequate volume of blood was collected at euthanasia, a complete blood count was performed on individual animals from the AE and SC studies. Group mean results are shown in Fig. 3. Significant variation among individuals was observed, which resulted in large standard deviations in some groups. However, in AE infected animals, there was a general decrease in the total number of white blood cells (WBC) (leukopenia) by 2 dpi, with the group mean value dropping below the normal (control group) range and remaining low through the end of the study. This decrease in WBCs was characterized by a decrease in lymphocytes (lymphopenia), while the number of neutrophils and monocytes (Fig. 3a-d), as well as the number of eosinophils and basophils (data not shown), remained within the normal range. Significant differences (p < 0.05) were observed in total WBC and number of lymphocytes between infected and uninfected animals from 12 hpi through the end of the study (Table 2). Interestingly, while the mean total number of neutrophils in infected animals never fell below the normal range at any time point, there were significant differences in the total number of neutrophils present in infected and uninfected animals at every time point. There were also significant differences in the number of platelets at 0.25 dpi and 0.5 dpi hpi. A leukopenia was also observed in SC infected animals; however, this occurred earlier, at 1 dpi, and when evaluating group means, was characterized by both a lymphopenia as well as a neutropenia. These values remained low through 2 dpi for lymphocytes and 3 dpi for neutrophils, after which time all mean values returned to the normal range for the remainder of the study. No significant differences between SC infected and uninfected animals were observed at any of the time points. The AE and SC group mean values for red blood cells remained within the normal range for the duration of the study.Fig. 3

Bottom Line: The majority of those animals exposed by the aerosol route developed severe clinical signs by 4 dpi.Significant differences were also observed in the viral titers of target tissues, with virus being detected in the brain at 6 hpi in the aerosol study.Aerosol exposure to EEEV results in acute onset of clinical signs, rapid neuroinvasion, and 100 % mortality.

View Article: PubMed Central - PubMed

Affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, 21702, USA. shelley.p.honnold.mil@mail.mil.

ABSTRACT

Background: Eastern equine encephalitis virus (EEEV), an arbovirus, is an important human and veterinary pathogen belonging to one of seven antigenic complexes in the genus Alphavirus, family Togaviridae. EEEV is considered the most deadly of the mosquito-borne alphaviruses due to the high case fatality rate associated with clinical infections, reaching up to 75 % in humans and 90 % in horses. In patients that survive acute infection, neurologic sequelae are often devastating. Although natural infections are acquired by mosquito bite, EEEV is also highly infectious by aerosol. This fact, along with the relative ease of production and stability of this virus, has led it to being identified as a potential agent of bioterrorism.

Methods: To characterize the clinical course and outcome of EEEV strain FL93-939 infection, we compared clinical parameters, cytokine expression, viremia, and viral titers in numerous tissues of mice exposed by various routes. Twelve-week-old female BALB/c mice were infected by the intranasal, aerosol, or subcutaneous route. Mice were monitored for clinical signs of disease and euthanized at specified time points (6 hpi through 8 dpi). Blood and tissues were harvested for cytokine analysis and/or viral titer determination.

Results: Although all groups of animals exhibited similar clinical signs after inoculation, the onset and severity differed. The majority of those animals exposed by the aerosol route developed severe clinical signs by 4 dpi. Significant differences were also observed in the viral titers of target tissues, with virus being detected in the brain at 6 hpi in the aerosol study.

Conclusion: The clinical course and outcome of EEEV infection in mice is dependent on route of exposure. Aerosol exposure to EEEV results in acute onset of clinical signs, rapid neuroinvasion, and 100 % mortality.

No MeSH data available.


Related in: MedlinePlus