title: Mouse model for the Rift Valley fever virus MP12 strain infection.
abstract: Rift Valley fever virus (RVFV), a Category A pathogen and select agent, is the causative agent of Rift Valley fever. To date, no fully licensed vaccine is available in the U.S. for human or animal use and effective antiviral drugs have not been identified. The RVFV MP12 strain is conditionally licensed for use for veterinary purposes in the U.S. which was excluded from the select agent rule of Health and Human Services and the U.S. Department of Agriculture. The MP12 vaccine strain is commonly used in BSL-2 laboratories that is generally not virulent in mice. To establish a small animal model that can be used in a BSL-2 facility for antiviral drug development, we investigated susceptibility of six mouse strains (129S6/SvEv, STAT-1 KO, 129S1/SvlmJ, C57BL/6J, NZW/LacJ, BALB/c) to the MP12 virus infection via an intranasal inoculation route. Severe weight loss, obvious clinical and neurologic signs, and 50% mortality was observed in the STAT-1 KO mice, whereas the other 5 mouse strains did not display obvious and/or severe disease. Virus replication and histopathological lesions were detected in brain and liver of MP12-infected STAT-1 KO mice that developed the acute-onset hepatitis and delayed-onset encephalitis. In conclusion, the STAT-1 KO mouse strain is susceptible to MP12 virus infection, indicating that it can be used to investigate RVFV antivirals in a BSL-2 environment.
authors: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors: Yuekun
authors: Y
authors: Lang
authors: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors: Jamie
authors: J
authors: Henningson
authors: USDA, ARS, Arthropod-Borne Animal Diseases Research Unit (ABADRU), Center for Grain and Animal Health Research, Manhattan, KS, USA.
authors: Dane
authors: D
authors: Jasperson
authors: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors: Yonghai
authors: Y
authors: Li
authors: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors: Jinhwa
authors: J
authors: Lee
authors: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors: Jingjiao
authors: J
authors: Ma
authors: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors: Yuhao
authors: Y
authors: Li
authors: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors: Nan
authors: N
authors: Cao
authors: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors: Haixia
authors: H
authors: Liu
authors: USDA, ARS, Arthropod-Borne Animal Diseases Research Unit (ABADRU), Center for Grain and Animal Health Research, Manhattan, KS, USA.
authors: William
authors: W
authors: Wilson
authors: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA.
authors: Juergen
authors: J
authors: Richt
authors: USDA, ARS, Arthropod-Borne Animal Diseases Research Unit (ABADRU), Center for Grain and Animal Health Research, Manhattan, KS, USA.
authors: Mark
authors: M
authors: Ruder
authors: USDA, ARS, Arthropod-Borne Animal Diseases Research Unit (ABADRU), Center for Grain and Animal Health Research, Manhattan, KS, USA.
authors: Scott
authors: S
authors: McVey
authors: Department of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, KS, USA. Electronic address: wma@vet.k-state.edu.
authors: Wenjun
authors: W
authors: Ma
mesh_terms: D000818:Animals; D001921:Brain / Q000821:virology; D004195:Disease Models, Animal; D008099:Liver / Q000821:virology; D051379:Mice; D008815:Mice, Inbred Strains; D012295:Rift Valley Fever / Q000821:virology*; D012296:Rift Valley fever virus / Q000145:classification*; D014779:Virus Replication / Q000502:physiology
keywords: MP12 vaccine strain; Mouse model; Rift Valley fever virus