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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

Geometric mean virus titer in the left and right gastrocnemius muscle and popliteal lymph node of individual BALB/c mice infected SC with EEEV strain FL93-939 in the left rear footpad (n = 5). Viral titers of tissue homogenate supernatants were determined by standard plaque assay. Symbols represent individual animals with values calculated from the geometric mean titer of all dilutions which had at least one visible pfu. The mean for the group is shown in the colored dashed line. The limit of detection of the assay is 5 pfu/ml tissue homogenate supernatant
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Fig8: Geometric mean virus titer in the left and right gastrocnemius muscle and popliteal lymph node of individual BALB/c mice infected SC with EEEV strain FL93-939 in the left rear footpad (n = 5). Viral titers of tissue homogenate supernatants were determined by standard plaque assay. Symbols represent individual animals with values calculated from the geometric mean titer of all dilutions which had at least one visible pfu. The mean for the group is shown in the colored dashed line. The limit of detection of the assay is 5 pfu/ml tissue homogenate supernatant

Mentions: Virus titers were determined for the left and right gastrocnemius muscle (calf muscle), a large muscle group in the lower leg, as it has been previously reported that EEEV replicates in skeletal muscle [10]. The mean viral titer of left gastrocnemius muscle remained low throughout the study and virus did not appear in the right gastrocnemius muscle until 5 dpi (Fig. 8). Virus titers were also determined for the left and right popliteal lymph nodes, the draining lymph nodes of the inoculation site. The mean virus titer of the left popliteal lymph node rose rapidly post-inoculation and remained at high levels until 6 dpi. While virus was detected in the right popliteal lymph node 1 dpi, viral titers were more sporadic and generally remained low throughout the study.Fig. 8


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)

Geometric mean virus titer in the left and right gastrocnemius muscle and popliteal lymph node of individual BALB/c mice infected SC with EEEV strain FL93-939 in the left rear footpad (n = 5). Viral titers of tissue homogenate supernatants were determined by standard plaque assay. Symbols represent individual animals with values calculated from the geometric mean titer of all dilutions which had at least one visible pfu. The mean for the group is shown in the colored dashed line. The limit of detection of the assay is 5 pfu/ml tissue homogenate supernatant
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig8: Geometric mean virus titer in the left and right gastrocnemius muscle and popliteal lymph node of individual BALB/c mice infected SC with EEEV strain FL93-939 in the left rear footpad (n = 5). Viral titers of tissue homogenate supernatants were determined by standard plaque assay. Symbols represent individual animals with values calculated from the geometric mean titer of all dilutions which had at least one visible pfu. The mean for the group is shown in the colored dashed line. The limit of detection of the assay is 5 pfu/ml tissue homogenate supernatant
Mentions: Virus titers were determined for the left and right gastrocnemius muscle (calf muscle), a large muscle group in the lower leg, as it has been previously reported that EEEV replicates in skeletal muscle [10]. The mean viral titer of left gastrocnemius muscle remained low throughout the study and virus did not appear in the right gastrocnemius muscle until 5 dpi (Fig. 8). Virus titers were also determined for the left and right popliteal lymph nodes, the draining lymph nodes of the inoculation site. The mean virus titer of the left popliteal lymph node rose rapidly post-inoculation and remained at high levels until 6 dpi. While virus was detected in the right popliteal lymph node 1 dpi, viral titers were more sporadic and generally remained low throughout the study.Fig. 8

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