For many viral infections, resolution of illness is associ-ated with long-term host control of viremia rather than viral eradication. An example is EBV infection, and the fact that host immune suppression is associated with EBV-induced disease suggests that it is the immune system that is holding the virus in check (1, 2). Other viruses are typically associated with progressive uncontrolled disease, and represent an expanding global problem. Over 30 million persons are estimated to be infected with HIV-1 (3), and HCV infection involves 4–6% of the population in certain geographic regions of the world (4). Understanding the correlates of immune protection against such progressive viral infections and the development of effective vaccines thus has great urgency.

Data from both human studies and murine models suggest that CTLs are an important host defense against viruses. CTLs recognize viral peptides that are processed intracellularly and presented at the cell surface as a trimolecular complex with 2-microglobulin and HLA class I. The fact that infected cells can be lysed before the production of progeny virions is indicative of the potency of these cells, at least under idealized laboratory conditions (5). In addition to lysis, recognition of infected cells through the epitope-specific TCR also leads to release of soluble antiviral factors (6). In HBV infection, both TNF-and IFN-have been shown to lead to clearance of virus from infected hepatocytes in a transgenic mouse model (7, 8). In HIV-1 infection, CTL activation by cognate epitope leads to secretion of macrophage inflammatory protein (MIP)-1, MIP-1, and RANTES (9, 10). These antiviral chemokines are localized within cytotoxic granules as a complex with sulfated proteoglycans, and are coordinately secreted with granzymes and perforin, thus exposing the microenvironment of the infected cell with antiviral factors that may serve to inhibit progeny that have already been produced (10).