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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

Change in average body temperature (a), and activity (b) after intranasal, aerosol, or subcutaneous infection with NA EEEV strain FL93-939. Body temperatures and activity were recorded for a 20 sec period every 30 min via an intraperitoneal telemetry device before and after infection with EEEV strain FL93-939. Values represent the average within the cohort (intranasal n = 5; aerosol n = 5; subcutaneous n = 9; control n = 15). 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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Fig2: Change in average body temperature (a), and activity (b) after intranasal, aerosol, or subcutaneous infection with NA EEEV strain FL93-939. Body temperatures and activity were recorded for a 20 sec period every 30 min via an intraperitoneal telemetry device before and after infection with EEEV strain FL93-939. Values represent the average within the cohort (intranasal n = 5; aerosol n = 5; subcutaneous n = 9; control n = 15). 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: Temperature and activity data were collected from EEEV infected and uninfected BALB/c mice to evaluate differences between various routes of infection and age-matched controls. The average daily temperature range was 35.2 - 37.8 °C. The mean temperature profile for each group is shown in Fig. 2a. The diurnal temperature pattern in IN and AE EEEV infected mice began to deviate from the pattern observed in control mice approximately 3–4 dpi, which coincided with onset of clinical signs. In SC infected animals, the diurnal temperature pattern was unchanged until 6–7 dpi, which coincided with the time at which the highest percentage of animals displayed clinical signs. The fever, detected by telemetry at 3 dpi for the IN and AE studies and 5 dpi in the SC study (Table 1), was the first indication that telemetric analysis coincided with the daily cage-side observations in detecting onset of disease. However, when comparing infected to uninfected mice within each study, only the infected animals in the AE and SC studies showed a significant difference in the duration and total fever hours relative to uninfected controls (p < 0.05), which may be a result of the small group numbers. In the AE study, 4 of 5 animals had a fever of significant duration; however, in the IN study only 3 of 5 animals had a fever for 2 or more consecutive time points. Nevertheless, the p-value in the IN study was just slightly above 0.05 for both duration and total fever hours (p = 0.08 for duration and p = 0.09 for total fever hours).Fig. 2


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)

Change in average body temperature (a), and activity (b) after intranasal, aerosol, or subcutaneous infection with NA EEEV strain FL93-939. Body temperatures and activity were recorded for a 20 sec period every 30 min via an intraperitoneal telemetry device before and after infection with EEEV strain FL93-939. Values represent the average within the cohort (intranasal n = 5; aerosol n = 5; subcutaneous n = 9; control n = 15). 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

Fig2: Change in average body temperature (a), and activity (b) after intranasal, aerosol, or subcutaneous infection with NA EEEV strain FL93-939. Body temperatures and activity were recorded for a 20 sec period every 30 min via an intraperitoneal telemetry device before and after infection with EEEV strain FL93-939. Values represent the average within the cohort (intranasal n = 5; aerosol n = 5; subcutaneous n = 9; control n = 15). 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: Temperature and activity data were collected from EEEV infected and uninfected BALB/c mice to evaluate differences between various routes of infection and age-matched controls. The average daily temperature range was 35.2 - 37.8 °C. The mean temperature profile for each group is shown in Fig. 2a. The diurnal temperature pattern in IN and AE EEEV infected mice began to deviate from the pattern observed in control mice approximately 3–4 dpi, which coincided with onset of clinical signs. In SC infected animals, the diurnal temperature pattern was unchanged until 6–7 dpi, which coincided with the time at which the highest percentage of animals displayed clinical signs. The fever, detected by telemetry at 3 dpi for the IN and AE studies and 5 dpi in the SC study (Table 1), was the first indication that telemetric analysis coincided with the daily cage-side observations in detecting onset of disease. However, when comparing infected to uninfected mice within each study, only the infected animals in the AE and SC studies showed a significant difference in the duration and total fever hours relative to uninfected controls (p < 0.05), which may be a result of the small group numbers. In the AE study, 4 of 5 animals had a fever of significant duration; however, in the IN study only 3 of 5 animals had a fever for 2 or more consecutive time points. Nevertheless, the p-value in the IN study was just slightly above 0.05 for both duration and total fever hours (p = 0.08 for duration and p = 0.09 for total fever hours).Fig. 2

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