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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 mean body weight (a) and percent of BALB/c mice that either displayed clinical signs of disease or were moribund (b) after intranasal, aerosol, or subcutaneous infection with EEEV strain FL93-939. Mice were monitored daily after infection and percent change in weight was determined from the day of infection (day 0). Note that the aerosol study was terminated at 4 dpi because 90 % of the animals in the 5 dpi group had moderate to severe signs of clinical disease. (*) Three animals in the subcutaneous study from the 8 dpi group were euthanized prematurely due to the onset of severe clinical disease
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Fig1: Change in mean body weight (a) and percent of BALB/c mice that either displayed clinical signs of disease or were moribund (b) after intranasal, aerosol, or subcutaneous infection with EEEV strain FL93-939. Mice were monitored daily after infection and percent change in weight was determined from the day of infection (day 0). Note that the aerosol study was terminated at 4 dpi because 90 % of the animals in the 5 dpi group had moderate to severe signs of clinical disease. (*) Three animals in the subcutaneous study from the 8 dpi group were euthanized prematurely due to the onset of severe clinical disease

Mentions: The post-exposure weight variance and onset of clinical signs following IN and AE exposure were similar (Fig. 1). Both groups of mice continued to gain weight up to 2 dpi. However, the IN group began to lose weight by 3 dpi, while the AE group had minimal increases in weight over the same time period. For both groups, there was rapid weight loss from 3 dpi to 4 dpi and the IN group continued to lose weight through the end of the study, 5 dpi. The AE study was terminated on 4 dpi because 90 % of the animals that were scheduled to be euthanized at 5 dpi were showing moderate to severe signs of clinical disease. In both the IN and AE studies, mice began displaying clinical signs of disease (ruffled fur, lethargy, hunched posture) at 3 dpi and both the percentage of animals affected and the severity of clinical signs increased from 3 dpi to the study endpoints. More severe clinical signs of disease included weight loss, dehydration, head tilt, circling, head tremors, focal muscle twitching, lateral recumbency, and rarely seizures.Fig. 1


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 mean body weight (a) and percent of BALB/c mice that either displayed clinical signs of disease or were moribund (b) after intranasal, aerosol, or subcutaneous infection with EEEV strain FL93-939. Mice were monitored daily after infection and percent change in weight was determined from the day of infection (day 0). Note that the aerosol study was terminated at 4 dpi because 90 % of the animals in the 5 dpi group had moderate to severe signs of clinical disease. (*) Three animals in the subcutaneous study from the 8 dpi group were euthanized prematurely due to the onset of severe clinical disease
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Change in mean body weight (a) and percent of BALB/c mice that either displayed clinical signs of disease or were moribund (b) after intranasal, aerosol, or subcutaneous infection with EEEV strain FL93-939. Mice were monitored daily after infection and percent change in weight was determined from the day of infection (day 0). Note that the aerosol study was terminated at 4 dpi because 90 % of the animals in the 5 dpi group had moderate to severe signs of clinical disease. (*) Three animals in the subcutaneous study from the 8 dpi group were euthanized prematurely due to the onset of severe clinical disease
Mentions: The post-exposure weight variance and onset of clinical signs following IN and AE exposure were similar (Fig. 1). Both groups of mice continued to gain weight up to 2 dpi. However, the IN group began to lose weight by 3 dpi, while the AE group had minimal increases in weight over the same time period. For both groups, there was rapid weight loss from 3 dpi to 4 dpi and the IN group continued to lose weight through the end of the study, 5 dpi. The AE study was terminated on 4 dpi because 90 % of the animals that were scheduled to be euthanized at 5 dpi were showing moderate to severe signs of clinical disease. In both the IN and AE studies, mice began displaying clinical signs of disease (ruffled fur, lethargy, hunched posture) at 3 dpi and both the percentage of animals affected and the severity of clinical signs increased from 3 dpi to the study endpoints. More severe clinical signs of disease included weight loss, dehydration, head tilt, circling, head tremors, focal muscle twitching, lateral recumbency, and rarely seizures.Fig. 1

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