A COMPARISON OF THE PATHOGENESIS OF CHIKUNGUNYA VIRUS IN MICE AFTER INFECTION BY MOSQUITO BITE OR NEEDLE INOCULATION

Sarah A. Ziegler, A.P.A. Travassos da Rosa, S.Y. Xiao, M.D., D. Vanlandingham, Ph.D., S. Higgs, Ph.D. and R. B. Tesh, M.D.

Department of Pathology, UTMB

Background: Chikungunya virus (CHIKV) is a mosquito-transmitted Alphavirus that causes an illness characterized by fever, rash, and incapacitating joint and muscle pain; the disease isendemic and sporadically epidemic in Asia and Africa. The pathogenesis of CHIKV in humans is not well understood. To gain a better understanding of CHIKV pathogenesis, a mouse model for CHIKV infection was recently developed in our laboratory. Previous work demonstrated that needle inoculation of CHIKV in young mice causes a self-limiting infection characterized by 3-4 days of viremia and persistence of virus in the skeletal muscle and spleen. Recent work has shown that the disease course is different if mosquito bite, rather than needle inoculation, is used to infect mice. Methods: CHIKV infected Ae. Aegypti mosquitoes were allowed to feed on young CD-1 mice. Groups of five mosquitoes were exposed to an anesthetized mouse, approximately five days after intrathoracic injection. In comparison to needle-inoculated young mice, the peak viremia levels in the mosquito-infected mice were 10-fold higher, but approximately 1-2 days shorter. In addition, differences in virus load were also observed in leg muscle and spleen. At day five, only one mouse out of three had detectable virus levels in the leg muscle in the mosquito-infected group; but, in the needle-inoculated group at day five, every mouse had greater than 104 PFU/mL of virus in the leg muscle. Also, in the mosquito-inoculated group, the viral load in the spleen was of shorter duration as compared to the needle-inoculated group. Conclusions: These preliminary results are the first to show a difference in virus titers and tropism between infection by mosquito bite and needle-inoculation of CHIKV in mice. Supported by the Department of Pathology and NIH contracts N01-AI25489 and N01-AI30027.