title: Pathogenesis of Lassa fever in cynomolgus macaques.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Virology, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Hensley
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: Joan B
authors.initials: JB
authors.lastname: Geisbert
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Fritz
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Daddario-DiCaprio
authors.forename: Tom
authors.initials: T
authors.lastname: Larsen
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Geisbert
mesh_terms: D032761:Animal Experimentation; D000825:Animal Structures / Q000473:pathology / Q000821:virology; D000818:Animals; D007150:Immunohistochemistry; D007835:Lassa Fever / Q000473:pathology / Q000662:veterinary* / Q000821:virology; D007836:Lassa virus / Q000472:pathogenicity*; D008252:Macaca fascicularis; D008853:Microscopy; D018419:Primate Diseases / Q000473:pathology* / Q000821:virology*