Limits...
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.

Show MeSH

Related in: MedlinePlus

Immunohistochemistry and TUNEL staining in lymphoid tissues of cynomolgus monkeys. (A) Immunopositive endothelial cells (brown) in an axillary lymph node at day 13. (B) Immunopositive tissue macrophages and dendritic cells (brown) in spleen at day 7. (C) TUNEL-positive (brown) lymphocytes and scattered tingible body macrophages in an axillary lymph node at day 7. (D) TUNEL-positive (brown) lymphocytes and scattered tingible body macrophages in an axillary lymph node at day 17. (E) Immunopositive tissue macrophages, endothelial cells, and dendritic cells (brown) in spleen at day 13. Inset is enlargement of indicated area (arrow) showing dendritic cell. (F) Immunopositive dendritic cells (brown) in thymus at day 7. Original magnifications, ×40 (A), ×20 (C, F), ×10 (B, D, F).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3104370&req=5

Figure 6: Immunohistochemistry and TUNEL staining in lymphoid tissues of cynomolgus monkeys. (A) Immunopositive endothelial cells (brown) in an axillary lymph node at day 13. (B) Immunopositive tissue macrophages and dendritic cells (brown) in spleen at day 7. (C) TUNEL-positive (brown) lymphocytes and scattered tingible body macrophages in an axillary lymph node at day 7. (D) TUNEL-positive (brown) lymphocytes and scattered tingible body macrophages in an axillary lymph node at day 17. (E) Immunopositive tissue macrophages, endothelial cells, and dendritic cells (brown) in spleen at day 13. Inset is enlargement of indicated area (arrow) showing dendritic cell. (F) Immunopositive dendritic cells (brown) in thymus at day 7. Original magnifications, ×40 (A), ×20 (C, F), ×10 (B, D, F).

Mentions: LASV antigen was frequently detected in dendritic cells of all lymph nodes of all animals (3/3) at day 7 and rarely detected in endothelial cells of 2/3 animals at day 7. Sinus histiocytosis and mild lymphocytolysis was seen in some, but not all lymph nodes in the three animals euthanized at this time point. By terminal time points (days 13.5-17) there was less extensive immunopositive staining of dendritic cells in all lymph nodes of all three animals. Increased numbers of immunopositive endothelial cells were detected in all lymph nodes of all terminal animals (3/3) (Figure 6A). An increase in TUNEL-positive lymphocytes and scattered tingible body macrophages with cytoplasmic TUNEL-positive debris was observed in the axillary lymph node of 1/3 terminal animals (Figure 6D) when compared with day 7 animals (Figure 6C). However, TUNEL results from inguinal and mesenteric lymph nodes were inconclusive.


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)

Immunohistochemistry and TUNEL staining in lymphoid tissues of cynomolgus monkeys. (A) Immunopositive endothelial cells (brown) in an axillary lymph node at day 13. (B) Immunopositive tissue macrophages and dendritic cells (brown) in spleen at day 7. (C) TUNEL-positive (brown) lymphocytes and scattered tingible body macrophages in an axillary lymph node at day 7. (D) TUNEL-positive (brown) lymphocytes and scattered tingible body macrophages in an axillary lymph node at day 17. (E) Immunopositive tissue macrophages, endothelial cells, and dendritic cells (brown) in spleen at day 13. Inset is enlargement of indicated area (arrow) showing dendritic cell. (F) Immunopositive dendritic cells (brown) in thymus at day 7. Original magnifications, ×40 (A), ×20 (C, F), ×10 (B, D, F).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Immunohistochemistry and TUNEL staining in lymphoid tissues of cynomolgus monkeys. (A) Immunopositive endothelial cells (brown) in an axillary lymph node at day 13. (B) Immunopositive tissue macrophages and dendritic cells (brown) in spleen at day 7. (C) TUNEL-positive (brown) lymphocytes and scattered tingible body macrophages in an axillary lymph node at day 7. (D) TUNEL-positive (brown) lymphocytes and scattered tingible body macrophages in an axillary lymph node at day 17. (E) Immunopositive tissue macrophages, endothelial cells, and dendritic cells (brown) in spleen at day 13. Inset is enlargement of indicated area (arrow) showing dendritic cell. (F) Immunopositive dendritic cells (brown) in thymus at day 7. Original magnifications, ×40 (A), ×20 (C, F), ×10 (B, D, F).
Mentions: LASV antigen was frequently detected in dendritic cells of all lymph nodes of all animals (3/3) at day 7 and rarely detected in endothelial cells of 2/3 animals at day 7. Sinus histiocytosis and mild lymphocytolysis was seen in some, but not all lymph nodes in the three animals euthanized at this time point. By terminal time points (days 13.5-17) there was less extensive immunopositive staining of dendritic cells in all lymph nodes of all three animals. Increased numbers of immunopositive endothelial cells were detected in all lymph nodes of all terminal animals (3/3) (Figure 6A). An increase in TUNEL-positive lymphocytes and scattered tingible body macrophages with cytoplasmic TUNEL-positive debris was observed in the axillary lymph node of 1/3 terminal animals (Figure 6D) when compared with day 7 animals (Figure 6C). However, TUNEL results from inguinal and mesenteric lymph nodes were inconclusive.

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