title: Development of a small animal peripheral challenge model of Japanese encephalitis virus using interferon deficient AG129 mice and the SA14-14-2 vaccine virus strain.
abstract: Japanese encephalitis virus (JEV) is the most common cause of viral encephalitis in Asia, and it is increasingly a global public health concern due to its recent geographic expansion. While commercial vaccines are available and used in some endemic countries, JEV continues to be a public health problem, with 50,000 cases reported annually. Research with virulent JEV in mouse models to develop new methods of prevention and treatment is restricted to BSL-3 containment facilities, confining these studies to investigators with access to these facilities. We have developed an adult small animal peripheral challenge model using interferon-deficient AG129 mice and the JEV live-attenuated vaccine SA14-14-2, thus requiring only BSL-2 containment. A low dose of virus (10PFU/0.1ml) induced 100% morbidity in infected mice. Increased body temperatures measured by implantable temperature transponders correlated with an increase in infectious virus and viral RNA in serum, spleen and brain as well as an increase in pro-inflammatory markers measured by a 58-biomarker multi-analyte profile (MAP) constructed during the course of infection. In the future, the MAP measurements can be used as a baseline for comparison in order to better assess the inhibition of disease progression by other prophylactic and therapeutic agents. The use of the AG129/JEV SA14-14-2 animal model makes vaccine and therapeutic studies feasible for laboratories with limited biocontainment facilities.
authors.affiliation: Arboviral Diseases Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USA. Electronic address: zpz0@cdc.gov.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Calvert
authors.affiliation: Arboviral Diseases Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USA.
authors.forename: Kandice L
authors.initials: KL
authors.lastname: Dixon
authors.affiliation: Arboviral Diseases Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Delorey
authors.affiliation: Arthropod-Borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Carol D
authors.initials: CD
authors.lastname: Blair
authors.affiliation: Arboviral Diseases Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Roehrig
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004664:Encephalitis Virus, Japanese / Q000145:classification; D004672:Encephalitis, Japanese / Q000517:prevention & control*; D007372:Interferons / Q000172:deficiency; D022321:Japanese Encephalitis Vaccines / Q000008:administration & dosage*; D051379:Mice; D014613:Vaccines, Attenuated / Q000008:administration & dosage; D019562:Viral Load
chemical_list: D022321:Japanese Encephalitis Vaccines; D014613:Vaccines, Attenuated; D007372:Interferons
keywords: AG129 mouse model; Flavivirus; Flavivirus pathogenesis; Interferon-deficient mice; JEV SA14-14-2 vaccine strain; Japanese encephalitis virus; Viral encephalitis