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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

Representative gross necropsy lesions from nonhuman primates experimentally infected with Lassa virus. (A) Enlargement and moderate congestion of mesenteric lymph nodes (arrows) at day 15. (B) Accumulation of fluid in the pericardial cavity of a cynomolgus monkey 17 days after infection with Lassa virus. (C) Reticulation and discoloration of the liver 15 days after infection with Lassa virus. (D) Multifocal red foci that microscopically corresponded with inflammation on the mucosal surface of the urinary bladder at day 15. (E) Congestion/hemorrhage of the cecum occurring at day 15. The cecum is opened up and the ileum extends outward from the cecum; arrow indicates the ileocecal junction.
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Figure 3: Representative gross necropsy lesions from nonhuman primates experimentally infected with Lassa virus. (A) Enlargement and moderate congestion of mesenteric lymph nodes (arrows) at day 15. (B) Accumulation of fluid in the pericardial cavity of a cynomolgus monkey 17 days after infection with Lassa virus. (C) Reticulation and discoloration of the liver 15 days after infection with Lassa virus. (D) Multifocal red foci that microscopically corresponded with inflammation on the mucosal surface of the urinary bladder at day 15. (E) Congestion/hemorrhage of the cecum occurring at day 15. The cecum is opened up and the ileum extends outward from the cecum; arrow indicates the ileocecal junction.

Mentions: At day 7, axillary and inguinal lymphadenopathy and congestion were observed in all three animals (3/3) euthanized at this time point. The mandibular and mesenteric lymph nodes were also enlarged (3/3) and noticeable enlargement and congestion of the iliac lymph nodes was noted in one of the day 7 macaques. Additional findings at day 7 included friable spleens (1/3) and congestion at the ileocecal junction (1/3). By terminal time points (days 13.5-17), similar congestion and enlargement of the inguinal, axillary, mandibular, and mesenteric lymph nodes (Figure 3A) were also suggestive of LASV infection in all terminal animals (3/3). Other noteworthy findings at days 13.5-17 included: congested or pale yellow, friable livers (3/3) (Figure 3C); adrenal gland enlargement (1/3); pancreas enlargement (1/3); renal congestion (1/3); accumulation of red-tinged fluid in the pericardial sac (2/3) (Figure 3B); congestion at the ileocecal junction (1/3) (Figure 3E); and petechial hemorrhage on the mucosal surface of the urinary bladder (1/3) (Figure 3D).


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)

Representative gross necropsy lesions from nonhuman primates experimentally infected with Lassa virus. (A) Enlargement and moderate congestion of mesenteric lymph nodes (arrows) at day 15. (B) Accumulation of fluid in the pericardial cavity of a cynomolgus monkey 17 days after infection with Lassa virus. (C) Reticulation and discoloration of the liver 15 days after infection with Lassa virus. (D) Multifocal red foci that microscopically corresponded with inflammation on the mucosal surface of the urinary bladder at day 15. (E) Congestion/hemorrhage of the cecum occurring at day 15. The cecum is opened up and the ileum extends outward from the cecum; arrow indicates the ileocecal junction.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Representative gross necropsy lesions from nonhuman primates experimentally infected with Lassa virus. (A) Enlargement and moderate congestion of mesenteric lymph nodes (arrows) at day 15. (B) Accumulation of fluid in the pericardial cavity of a cynomolgus monkey 17 days after infection with Lassa virus. (C) Reticulation and discoloration of the liver 15 days after infection with Lassa virus. (D) Multifocal red foci that microscopically corresponded with inflammation on the mucosal surface of the urinary bladder at day 15. (E) Congestion/hemorrhage of the cecum occurring at day 15. The cecum is opened up and the ileum extends outward from the cecum; arrow indicates the ileocecal junction.
Mentions: At day 7, axillary and inguinal lymphadenopathy and congestion were observed in all three animals (3/3) euthanized at this time point. The mandibular and mesenteric lymph nodes were also enlarged (3/3) and noticeable enlargement and congestion of the iliac lymph nodes was noted in one of the day 7 macaques. Additional findings at day 7 included friable spleens (1/3) and congestion at the ileocecal junction (1/3). By terminal time points (days 13.5-17), similar congestion and enlargement of the inguinal, axillary, mandibular, and mesenteric lymph nodes (Figure 3A) were also suggestive of LASV infection in all terminal animals (3/3). Other noteworthy findings at days 13.5-17 included: congested or pale yellow, friable livers (3/3) (Figure 3C); adrenal gland enlargement (1/3); pancreas enlargement (1/3); renal congestion (1/3); accumulation of red-tinged fluid in the pericardial sac (2/3) (Figure 3B); congestion at the ileocecal junction (1/3) (Figure 3E); and petechial hemorrhage on the mucosal surface of the urinary bladder (1/3) (Figure 3D).

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