Characterization of the role of the innate immune system in the pathogenesis of chikungunya virus in mice

Chikungunya virus (CHIKV) is an alphavirus which causes a febrile illness in people that can induce a persistent and recurrent arthralgia. Recent outbreaks of CHIKV in tropical regions have caused millions of people debilitating illness. With no specific vaccine or anti-viral treatment, the development of an animal model and a better understanding of CHIKV pathogenesis is very important. The focus of my work was to develop a small animal model of CHIKV infection and to aid in elucidating the role of the immune system in CHIKV pathogenesis. Infecting young outbred mice resulted in an acute illness with severe myositis and inflammation in the skeletal muscle. This was used as a small animal model that aided in the study of the pathogenesis and the immune response of infected animals. By using GFP and luciferase bearing clones of CHIKV, it was found that the virus replicated in the lymph nodes and skeletal muscle of the mice. It was also shown that mosquito saliva, lower virus dose and footpad inoculation all cause decreased amounts of myositis as compared to needle inoculation in the skin of the back. Lastly, it was shown that certain immunosuppressants can decrease the disease severity of CHIKV infection in mice, while decreasing interferon increases disease severity and mortality in mice. Dexamethasone was studied as a possible treatment option for CHIKV infection and was found to cause a decrease in the disease severity in CHIKV-infected mice. Overall, this work has shown that the immune system plays a complex role during CHIKV infection in mice, both clearing the virus and causing disease related pathology. Interferon is important in controlling viral replication, but macrophages and neutrophils may be key mediators of CHIKV-induced myositis.

Name thesis:degree_name

Experimental Pathology (Doctoral)

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Virology

Grantor

The University of Texas Medical Branch at Galveston

Author dc:creator

• Ziegler, Sarah 1980-

Advisor dc:contributor.advisor

• Tesh, Robert B

Committee members dc:contributor.committeemember

• Higgs, Stephen
• Weaver, Scott
• Wikel, Stephen
• Powers, Ann

• chikungunya
• virus
• alphavirus
• mosquito

Handle dc:identifier.uri

http://hdl.handle.net/2152.3/785

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/785