THE DISTINCTIVE FEATURES OF INFLUENZA-VIRUS INFECTION OF DENDRITIC CELLS

CD8(+) cytolytic T lymphocytes (CTLs) are considered to be critical me diators for resistance to influenza virus infection. Me have previousl y demonstrated that dendritic cells are potent antigen presenting cell s in the development of antiinfluenza CTLs. Here we identify distincti ve features of the interaction of influenza virus with dendritic cells . Exposure of dendritic cells to influenza virus at MOIs bf 2-4:1 lead s to > 90% infection, as manifested by the expression of the viral pro teins HA and NS1. The infection is non-toxic as viral protein expressi on is sustained for > 2 days with retention of viability, but little i nfectious virus is produced. Substantial induction of the anti-viral c ytokine IFN-alpha also occurs. Influenza infection of macrophages also results in viral protein expression in a majority of cells, and synth esis of IFN-alpha. In contrast to dendritic cells, macrophages display evidence of apoptosis within 10-12 hours, and the majority of cells d ie within 24-36 hours. During this interval macrophages synthesize > 1 0-fold higher levels of virus than dendritic cells, Infected dendritic cells but not macrophages, can induce substantial CTL responses from purified blood CD8(+) T cells in the absence of exogenous cytokines su ch as IL-2. Low levels of infection (MOIs of 0.02) are sufficient to g enerate potent CTL responses. Influenza virus expressing non-cleaved H A does not elicit CTLs indicating that virus must access the cytoplasm of dendritic cells to utilize traditional class I processing pathways . These observations indicate that DCs are distinct in their handling of influenza virus and for the induction of anti-viral immunity.