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Pathogenesis of Lassa fever in cynomolgus macaques.

Hensley LE, Smith MA, Geisbert JB, Fritz EA, Daddario-DiCaprio KM, Larsen T, Geisbert TW - Virol. J. (2011)

Bottom Line: Tissues from three animals were examined at an early- to mid-stage of disease and compared with tissues from three animals collected at terminal stages of disease.Evidence of coagulopathy was noted; however, the degree of fibrin deposition in tissues was less prominent than has been reported in other viral hemorrhagic fevers.The sequence of pathogenic events identified in this study begins to shed light on the development of disease processes during Lassa fever and also may provide new targets for rational prophylactic and chemotherapeutic interventions.

View Article: PubMed Central - HTML - PubMed

Affiliation: Virology, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.

ABSTRACT

Background: Lassa virus (LASV) infection causes an acute and sometimes fatal hemorrhagic disease in humans and nonhuman primates; however, little is known about the development of Lassa fever. Here, we performed a pilot study to begin to understand the progression of LASV infection in nonhuman primates.

Methods: Six cynomolgus monkeys were experimentally infected with LASV. Tissues from three animals were examined at an early- to mid-stage of disease and compared with tissues from three animals collected at terminal stages of disease.

Results: Dendritic cells were identified as a prominent target of LASV infection in a variety of tissues in all animals at day 7 while Kupffer cells, hepatocytes, adrenal cortical cells, and endothelial cells were more frequently infected with LASV in tissues of terminal animals (days 13.5-17). Meningoencephalitis and neuronal necrosis were noteworthy findings in terminal animals. Evidence of coagulopathy was noted; however, the degree of fibrin deposition in tissues was less prominent than has been reported in other viral hemorrhagic fevers.

Conclusion: The sequence of pathogenic events identified in this study begins to shed light on the development of disease processes during Lassa fever and also may provide new targets for rational prophylactic and chemotherapeutic interventions.

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Related in: MedlinePlus

Cytokines and chemokines. Analysis of cytokine and chemokine accumulation in serum/plasma Lassa virus-infected cynomolgus monkeys.
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Figure 5: Cytokines and chemokines. Analysis of cytokine and chemokine accumulation in serum/plasma Lassa virus-infected cynomolgus monkeys.

Mentions: In order to evaluate the immune response to LASV infection, plasma and/or sera were analyzed for levels of cytokines/chemokines. Significant increases (p < 0.05) in levels of MCP-1 were detected at days 3, 5.5, 7, 10, and 13.5 while significant increases in levels of eotaxin were observed at days 3, 7, and 13.5 after LASV challenge (Figure 5). Significant increases in levels of IL-6 and IL-1β were detected at day 13.5 (Figure 5). Increased levels of IFN-α, IFN-γ, IL-1R, IL-2R, IL-4, IL-5, IL-7, IL-8, IL-10, IL-12 p40/p70, IL-13, IL-15, IL-17, IP-10, GM-CSF, MIG, RANTES, and TNF-α were not detected in any animal at any time point.


Pathogenesis of Lassa fever in cynomolgus macaques.

Hensley LE, Smith MA, Geisbert JB, Fritz EA, Daddario-DiCaprio KM, Larsen T, Geisbert TW - Virol. J. (2011)

Cytokines and chemokines. Analysis of cytokine and chemokine accumulation in serum/plasma Lassa virus-infected cynomolgus monkeys.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3104370&req=5

Figure 5: Cytokines and chemokines. Analysis of cytokine and chemokine accumulation in serum/plasma Lassa virus-infected cynomolgus monkeys.
Mentions: In order to evaluate the immune response to LASV infection, plasma and/or sera were analyzed for levels of cytokines/chemokines. Significant increases (p < 0.05) in levels of MCP-1 were detected at days 3, 5.5, 7, 10, and 13.5 while significant increases in levels of eotaxin were observed at days 3, 7, and 13.5 after LASV challenge (Figure 5). Significant increases in levels of IL-6 and IL-1β were detected at day 13.5 (Figure 5). Increased levels of IFN-α, IFN-γ, IL-1R, IL-2R, IL-4, IL-5, IL-7, IL-8, IL-10, IL-12 p40/p70, IL-13, IL-15, IL-17, IP-10, GM-CSF, MIG, RANTES, and TNF-α were not detected in any animal at any time point.

Bottom Line: Tissues from three animals were examined at an early- to mid-stage of disease and compared with tissues from three animals collected at terminal stages of disease.Evidence of coagulopathy was noted; however, the degree of fibrin deposition in tissues was less prominent than has been reported in other viral hemorrhagic fevers.The sequence of pathogenic events identified in this study begins to shed light on the development of disease processes during Lassa fever and also may provide new targets for rational prophylactic and chemotherapeutic interventions.

View Article: PubMed Central - HTML - PubMed

Affiliation: Virology, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.

ABSTRACT

Background: Lassa virus (LASV) infection causes an acute and sometimes fatal hemorrhagic disease in humans and nonhuman primates; however, little is known about the development of Lassa fever. Here, we performed a pilot study to begin to understand the progression of LASV infection in nonhuman primates.

Methods: Six cynomolgus monkeys were experimentally infected with LASV. Tissues from three animals were examined at an early- to mid-stage of disease and compared with tissues from three animals collected at terminal stages of disease.

Results: Dendritic cells were identified as a prominent target of LASV infection in a variety of tissues in all animals at day 7 while Kupffer cells, hepatocytes, adrenal cortical cells, and endothelial cells were more frequently infected with LASV in tissues of terminal animals (days 13.5-17). Meningoencephalitis and neuronal necrosis were noteworthy findings in terminal animals. Evidence of coagulopathy was noted; however, the degree of fibrin deposition in tissues was less prominent than has been reported in other viral hemorrhagic fevers.

Conclusion: The sequence of pathogenic events identified in this study begins to shed light on the development of disease processes during Lassa fever and also may provide new targets for rational prophylactic and chemotherapeutic interventions.

Show MeSH
Related in: MedlinePlus