Many viruses encode proteins whose major function is to evade or disable the host T cell response. Nevertheless, most viruses are readily detected by host T cells, and induce relatively strong T cell responses. Herein, we employ transgenic CD4 + and CD8 + T cells as sensors to evaluate in vitro and in vivo antigen presentation by coxsackievirus B3 (CVB3), and we show that this virus almost completely inhibits antigen presentation via the MHC class I pathway, thereby evading CD8 + T cell immunity. In contrast, the presentation of CVB3-encoded MHC class II epitopes is relatively unencumbered, and CVB3 induces in vivo CD4 + T cell responses that are, by several criteria, phenotypically normal. The cells display an effector phenotype and mature into multi-functional CVB3-specific memory CD4 + T cells that expand dramatically following challenge infection and rapidly differentiate into secondary effector cells capable of secreting multiple cytokines. Our findings have implications for the efficiency of antigen cross-presentation during coxsackievirus infection.
Many viruses—for example, large DNA viruses like smallpox virus and herpesviruses—encode several proteins whose major function is to combat the host's immune response, but these proteins usually battle in vain; in general, the mammalian immune system is sufficiently accomplished to penetrate this viral armor, allowing the infected animal to mount an immune response that can eradicate—or, at least, suppress—the infectious agent. Here, we show that coxsackievirus, a small RNA virus, carries a far more powerful punch than its larger DNA cousins; it almost entirely evades detection by host CD8 + T cells, which usually are one of the key components of an antiviral immune response. How does the virus achieve such success? Normally, when a virus infects a cell, certain host proteins capture small fragments of the virus and display them on the cell's surface, allowing them to be detected by the host immune system—usually, by cells called CD8 + T cells. We show here that coxsackievirus very effectively prevents these “flags” from reaching the cell surface in a form that can trigger naïve T cells to respond; in effect, the virus renders the cell “invisible” to CD8 + T cells, creating a cocoon in which the virus can multiply undisturbed by host immunity.