Virus evasion of host immune responses

The ability of arenaviruses to persist in their long-term carriers is facilitated by antigenic variation that allows evasion of host immune responses. Neutraliz-ation-resistant variants of Junin and Tacaribe viruses escape the humoral immune response, and certain epitope variants of LCMV escape the CTL response. In addition to viral variants that can escape host immune surveillance, variants have been described that suppress the immune response and thereby persist. Docile is a variant of the Aggressive isolate of LCMV (UBC), and Clone 13 is a variant of the LCMV (Armstrong strain). Both Docile and Clone 13 replicate very well in the spleen and poorly in the brain in contrast to their parental viruses. Both Docile and Clone 13 elicit poor CTL responses when tested 7 days after infection, and consequently, both persist in the mouse longer than their parental viruses. Docile and Clone 13 isolates actually do elicit CTL by day 3 after infection, but these viruses replicate so vigorously in the spleen that they cause high-dose immune suppression, i.e. high immune stimulation leading to massive apoptosis of immuno-cytes, leading to little CTL response by day 7. Thus, virus isolates that were thought to be immunosup-

pressive are in fact evading host immune responses by overstimulating and destroying the immune response.

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