Enterovirus 71 (EV71)
infection has induced fatal
encephalitis in thousands of young children in the Asia-Pacific region over 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 the brains of infected patients and mice, and they protect mice from
infection by decreasing the viral burden. The
chemokines responsible for recruiting lymphocytes to infected organs are yet 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 patients with brainstem
encephalitis as compared with the levels of a monokine induced by
gamma interferon (Mig). Using a murine model to investigate 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 titres in the blood and brain. Brain neurons of infected mice expressed IP-10. Using wild-type mice and IP-10 gene knockout mice to investigate the role of IP-10 in EV71
infection, we found that IP-10 deficiency significantly reduced levels of Mig in serum, and levels of
gamma interferon and the number of CD8 T cells in the mouse brain. Absence of IP-10 significantly increased the mortality of infected mice by 45%, with 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 the survival of mice.