title: The pathogenesis of Rift Valley fever virus in the mouse model.
abstract: Detailed studies describing the pathogenesis of Rift Valley fever (RVF) virus (RVFV) in the mouse model are lacking. A fully characterized small animal model of RVF is needed to evaluate potential vaccines and therapeutics. In this study, we characterized the pathogenesis of RVFV throughout the disease course in mice. Infection produced high-titer viremia and demonstrated RVFV tropism for a variety of tissue and individual cell types. Overwhelming infection of hepatocytes, accompanied by apoptosis, was a major consequence of infection. The majority of mice died or were euthanatized between days 3 and 6 postinfection with severe hepatitis. The remaining mice effectively cleared virus from the liver and blood, but exhibited neuroinvasion and developed panencephalitis. In addition, we characterized a number of other virological, clinicopathological, and histopathological features of RVFV infection in mice. The mouse model therefore mimics both the acute-onset hepatitis and delayed-onset encephalitis that are dominant features of severe human RVF.
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA. darci.smith1@us.army.mil
authors.forename: Darci R
authors.initials: DR
authors.lastname: Smith
authors.forename: Keith E
authors.initials: KE
authors.lastname: Steele
authors.forename: Joshua
authors.initials: J
authors.lastname: Shamblin
authors.forename: Anna
authors.initials: A
authors.lastname: Honko
authors.forename: Joshua
authors.initials: J
authors.lastname: Johnson
authors.forename: Christopher
authors.initials: C
authors.lastname: Reed
authors.forename: Maureen
authors.initials: M
authors.lastname: Kennedy
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Chapman
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Hensley
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology / Q000821:virology; D051379:Mice; D012295:Rift Valley Fever / Q000401:mortality / Q000473:pathology* / Q000821:virology; D012296:Rift Valley fever virus / Q000472:pathogenicity*; D014766:Viremia / Q000473:pathology / Q000821:virology
chemical_list: D000914:Antibodies, Viral