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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

Distribution of EEEV FL93-939 in fluids and tissues of BALB/c mice exposed by various routes. Shown are the geometric mean virus titer of individual animals in the serum (a), bronchoalveolar lavage (BAL) (b), nasopharyngeal flush (NF) (C) and brain (D) (n = 5/time point). Symbols represent individual animals with values calculated from the geometric mean titer of all dilutions which had at least one visible pfu by standard plaque assay. The mean for the group is shown in the colored dashed line. The limit of detection of the assay is 5 pfu/ml fluid or tissue homogenate supernatant
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Fig5: Distribution of EEEV FL93-939 in fluids and tissues of BALB/c mice exposed by various routes. Shown are the geometric mean virus titer of individual animals in the serum (a), bronchoalveolar lavage (BAL) (b), nasopharyngeal flush (NF) (C) and brain (D) (n = 5/time point). Symbols represent individual animals with values calculated from the geometric mean titer of all dilutions which had at least one visible pfu by standard plaque assay. The mean for the group is shown in the colored dashed line. The limit of detection of the assay is 5 pfu/ml fluid or tissue homogenate supernatant

Mentions: Viremia was first detected in the SC study at 12 hpi, while viremia was not detected until 1 dpi in either the IN or AE studies (Fig. 5a). This was likely due to the route of infection and rapid viral replication at the inoculation site. However, viremia remained low in the SC study and was not detected after 4 dpi. In contrast, while viremia appeared at 1 dpi in both the IN and AE studies, it peaked at 2 dpi, was substantially higher than the SC study, and was present until the study endpoint.Fig. 5


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)

Distribution of EEEV FL93-939 in fluids and tissues of BALB/c mice exposed by various routes. Shown are the geometric mean virus titer of individual animals in the serum (a), bronchoalveolar lavage (BAL) (b), nasopharyngeal flush (NF) (C) and brain (D) (n = 5/time point). Symbols represent individual animals with values calculated from the geometric mean titer of all dilutions which had at least one visible pfu by standard plaque assay. The mean for the group is shown in the colored dashed line. The limit of detection of the assay is 5 pfu/ml fluid or tissue homogenate supernatant
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig5: Distribution of EEEV FL93-939 in fluids and tissues of BALB/c mice exposed by various routes. Shown are the geometric mean virus titer of individual animals in the serum (a), bronchoalveolar lavage (BAL) (b), nasopharyngeal flush (NF) (C) and brain (D) (n = 5/time point). Symbols represent individual animals with values calculated from the geometric mean titer of all dilutions which had at least one visible pfu by standard plaque assay. The mean for the group is shown in the colored dashed line. The limit of detection of the assay is 5 pfu/ml fluid or tissue homogenate supernatant
Mentions: Viremia was first detected in the SC study at 12 hpi, while viremia was not detected until 1 dpi in either the IN or AE studies (Fig. 5a). This was likely due to the route of infection and rapid viral replication at the inoculation site. However, viremia remained low in the SC study and was not detected after 4 dpi. In contrast, while viremia appeared at 1 dpi in both the IN and AE studies, it peaked at 2 dpi, was substantially higher than the SC study, and was present until the study endpoint.Fig. 5

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