C3H/HeN mouse model for the evaluation of antiviral agents for the treatment of Venezuelan equine encephalitis virus infection.
The TC-83 vaccine strain of Venezuelan equine encephalitis virus (VEEV) causes encephalitis and death in C3H/HeN mice infected by intranasal (i.n.) instillation. Since TC-83 is exempt as a select agent, this mouse model was used in the evaluation of antiviral therapies. Virus titers in the brains of infected mice peaked on 4 dpi and persisted at high levels until death at 9.4+/-0.5 dpi. Mouse brains appeared histologically normal on 2 dpi, but developed meningoencephalitis, neuropil vacuolation, and gliosis by 8 dpi. Results from a protein cytokine array showed significant elevations over time in interleukin (IL)-1alpha, IL-1beta, IL-6, IL-12, MCP-1, IFNgamma, TNFalpha, MIP-1alpha, and RANTES in homogenized brain samples of infected mice. Immunohistochemical staining showed a colocalization of viral antigen with neuron markers. Treatment with interferon-alpha B/D or ampligen significantly improved survival, brain virus titer and cytokine levels, mean day-to-death, and weight change in infected mice. The time-course of infection and disease parameters of mice infected with TC-83 VEEV were similar in many ways to disease parameters in mice infected with other VEEV strains. Thus, infection of C3H/HeN mice with TC-83 VEEV may serve as a suitable model for the evaluation of antiviral compounds for the treatment of this viral disease.
Julander
Justin G
JG
Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, 5600 Old Main Hill, Logan, UT 84322-5600, United States. jgjulander@cc.usu.edu
Skirpstunas
Ramona
R
Siddharthan
Venkatraman
V
Shafer
Kristiina
K
Hoopes
Justin D
JD
Smee
Donald F
DF
Morrey
John D
JD
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000821:virology; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004666:Encephalitis Virus, Venezuelan Equine / Q000187:drug effects / Q000472:pathogenicity*; D004685:Encephalomyelitis, Venezuelan Equine / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D005260:Female; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D016896:Treatment Outcome; D014709:Vero Cells; D014765:Viral Vaccines
D000998:Antiviral Agents; D016207:Cytokines; D014765:Viral Vaccines