Enterovirus 71 (EV71) infection has induced fatal encephalitis in thousands of young children in the Asia-Pacific region since the last decade. EV71 infection continues to cause serious problems in areas with outbreaks, because vaccines and antiviral therapies are not available. Lymphocytes are present in brains of infected patients and mice and protect mice from infection by decreasing viral burden. The chemokines responsible for recruiting lymphocytes to infected organs remain to be identified. Among the lymphocyte chemokines detected, high levels of interferon-gamma-inducible protein-10 (IP-10) are found in the plasma and cerebral spinal fluid of patient with brainstem encephalitis as compared with monokine induced by gamma interferon (Mig). Using a murine model to address the induction of IP-10 by EV71 infection, we observed that EV71 infection significantly enhanced IP-10 protein expression in the serum and brain with kinetics similar to viral titers in the blood and brain. Brain neurons of infected mice expressed IP-10. Using wild-type mice and IP-10 gene knock-out mice to investigate the role of IP-10 in EV71 infection, we found that IP-10 deficiency significantly reduced levels of Mig in the serum and gamma interferon as well as CD8 T cells in the mouse brain. Absence of IP-10 significantly increased the mortality of infected mice by 45% with a slow virus clearance in several vital tissues. Our observations are consistent with a model where EV71 infection boosts IP-10 expression to increase gamma interferon and Mig levels, infiltration of CD8 T cells, virus clearance in tissues, and survival of mice.
Date:
2013-05
Relation:
Journal of General Virology. 2013 May;94(Pt 5):1019-1027.
