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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

Hematology and coagulation values after infection of cynomolgus monkeys with Lassa virus. Development of lymphopenia (top left panel) and thromobocytopenia (top right panel). Increases in circulating levels of D-dimers (bottom left panel) and decreases in circulating levels of activated protein C (bottom right panel).
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Figure 1: Hematology and coagulation values after infection of cynomolgus monkeys with Lassa virus. Development of lymphopenia (top left panel) and thromobocytopenia (top right panel). Increases in circulating levels of D-dimers (bottom left panel) and decreases in circulating levels of activated protein C (bottom right panel).

Mentions: There was a pronounced lymphopenia as lymphocytes dropped from approximately 59% of the leukocyte population just prior to LASV challenge (day 0) to less than 25% on day 3, and then appeared to slightly rebound to approximately 40% by day 10 (Figure 1). Although still within normal reference range, circulating platelet numbers declined from a mean of 392 × 10*/mm* (range 100-700 × 10*/mm*) before LASV challenge (day 0) to 205 × 10*/mm* on day 10 (Figure 1). However, by day 13.5, platelet numbers returned to pre-challenge levels (mean 414 × 10*/mm*). Development of fibrin degradation products (D-dimers) showed increases of 12-fold by day 7 and near 20-fold by day 10 (Figure 1). Plasma levels of protein C remained unchanged at day 3 but decreased by approximately 25% at days 7 and 10 (Figure 1).


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)

Hematology and coagulation values after infection of cynomolgus monkeys with Lassa virus. Development of lymphopenia (top left panel) and thromobocytopenia (top right panel). Increases in circulating levels of D-dimers (bottom left panel) and decreases in circulating levels of activated protein C (bottom right panel).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Hematology and coagulation values after infection of cynomolgus monkeys with Lassa virus. Development of lymphopenia (top left panel) and thromobocytopenia (top right panel). Increases in circulating levels of D-dimers (bottom left panel) and decreases in circulating levels of activated protein C (bottom right panel).
Mentions: There was a pronounced lymphopenia as lymphocytes dropped from approximately 59% of the leukocyte population just prior to LASV challenge (day 0) to less than 25% on day 3, and then appeared to slightly rebound to approximately 40% by day 10 (Figure 1). Although still within normal reference range, circulating platelet numbers declined from a mean of 392 × 10*/mm* (range 100-700 × 10*/mm*) before LASV challenge (day 0) to 205 × 10*/mm* on day 10 (Figure 1). However, by day 13.5, platelet numbers returned to pre-challenge levels (mean 414 × 10*/mm*). Development of fibrin degradation products (D-dimers) showed increases of 12-fold by day 7 and near 20-fold by day 10 (Figure 1). Plasma levels of protein C remained unchanged at day 3 but decreased by approximately 25% at days 7 and 10 (Figure 1).

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