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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

Clinical chemistry values after infection of cynomolgus monkeys with Lassa virus. Elevated levels of serum enzymes primarily at the late stages of disease (days 13-17). Top left panel, alanine aminotransferase (ALT). Top right panel, aspartate aminotransferase (AST). Bottom left panel, blood urea nitrogen (BUN).
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Figure 2: Clinical chemistry values after infection of cynomolgus monkeys with Lassa virus. Elevated levels of serum enzymes primarily at the late stages of disease (days 13-17). Top left panel, alanine aminotransferase (ALT). Top right panel, aspartate aminotransferase (AST). Bottom left panel, blood urea nitrogen (BUN).

Mentions: Early serum enzyme levels were unremarkable, but many were elevated during the late stages of disease. On day 10, aspartate aminotransferase (AST) increased nearly 3-fold (mean, 97 IU/L) as did alanine aminotransferase (ALT) (mean, 69 IU/L) by day 13.5 (Figure 2). Blood urea nitrogen (BUN) levels remained generally within normal limits through day 10 and increased nearly 2-fold over baseline on day 13.5 (Figure 2). Serum albumin levels slightly decreased from a pre-LASV challenge mean of 3.0 g/dL to 1.8 g/dL by day 17; however, total protein levels did not substantially fluctuate during the course of infection.


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)

Clinical chemistry values after infection of cynomolgus monkeys with Lassa virus. Elevated levels of serum enzymes primarily at the late stages of disease (days 13-17). Top left panel, alanine aminotransferase (ALT). Top right panel, aspartate aminotransferase (AST). Bottom left panel, blood urea nitrogen (BUN).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Clinical chemistry values after infection of cynomolgus monkeys with Lassa virus. Elevated levels of serum enzymes primarily at the late stages of disease (days 13-17). Top left panel, alanine aminotransferase (ALT). Top right panel, aspartate aminotransferase (AST). Bottom left panel, blood urea nitrogen (BUN).
Mentions: Early serum enzyme levels were unremarkable, but many were elevated during the late stages of disease. On day 10, aspartate aminotransferase (AST) increased nearly 3-fold (mean, 97 IU/L) as did alanine aminotransferase (ALT) (mean, 69 IU/L) by day 13.5 (Figure 2). Blood urea nitrogen (BUN) levels remained generally within normal limits through day 10 and increased nearly 2-fold over baseline on day 13.5 (Figure 2). Serum albumin levels slightly decreased from a pre-LASV challenge mean of 3.0 g/dL to 1.8 g/dL by day 17; however, total protein levels did not substantially fluctuate during the course of infection.

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