title: Development of a novel nonhuman primate model for Rift Valley fever.
abstract: Rift Valley fever (RVF) virus (RVFV) can cause severe human disease characterized by either acute-onset hepatitis, delayed-onset encephalitis, retinitis and blindness, or a hemorrhagic syndrome. The existing nonhuman primate (NHP) model for RVF utilizes an intravenous (i.v.) exposure route in rhesus macaques (Macaca mulatta). Severe disease in these animals is infrequent, and large cohorts are needed to observe significant morbidity and mortality. To overcome these drawbacks, we evaluated the infectivity and pathogenicity of RVFV in the common marmoset (Callithrix jacchus) by i.v., subcutaneous (s.c.), and intranasal exposure routes to more closely mimic natural exposure. Marmosets were more susceptible to RVFV than rhesus macaques and experienced higher rates of morbidity, mortality, and viremia and marked aberrations in hematological and chemistry values. An overwhelming infection of hepatocytes was a major consequence of infection of marmosets by the i.v. and s.c. exposure routes. Additionally, these animals displayed signs of hemorrhagic manifestations and neurological impairment. Based on our results, the common marmoset model more closely resembles severe human RVF disease and is therefore an ideal model for the evaluation of potential vaccines and therapeutics.
authors.affiliation: US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA. darci.smith1@us.army.mil
authors.forename: Darci R
authors.initials: DR
authors.lastname: Smith
authors.forename: Brian H
authors.initials: BH
authors.lastname: Bird
authors.forename: Bridget
authors.initials: B
authors.lastname: Lewis
authors.forename: Sara C
authors.initials: SC
authors.lastname: Johnston
authors.forename: Sarah
authors.initials: S
authors.lastname: McCarthy
authors.forename: Ashley
authors.initials: A
authors.lastname: Keeney
authors.forename: Miriam
authors.initials: M
authors.lastname: Botto
authors.forename: Ginger
authors.initials: G
authors.lastname: Donnelly
authors.forename: Joshua
authors.initials: J
authors.lastname: Shamblin
authors.forename: César G
authors.initials: CG
authors.lastname: Albariño
authors.forename: Stuart T
authors.initials: ST
authors.lastname: Nichol
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Hensley
mesh_terms: D000818:Animals; D002144:Callithrix; D004195:Disease Models, Animal; D006801:Humans; D008253:Macaca mulatta; D012295:Rift Valley Fever / Q000401:mortality / Q000821:virology*; D012296:Rift Valley fever virus / Q000472:pathogenicity / Q000502:physiology*; D014774:Virulence