However, epitopes of LCMV NP could be detected on the cell surface of LCMV-infected MC57G fibrosarcoma cells by flow cytometry using the LCMV NP specific mAb KL53 (Fig. 8B, left). The same result was obtained with selleck chemicals the LCMV NP specific mAb VL4 (data

not shown). The NP staining intensity was lower compared with staining with the LCMV GP-specific mAb KL25 (Fig. 8B, right) but nonetheless, it was clearly evident. Hence, epitopes of LCMV NP were present on the cell surface of infected cells and Abs specific for these epitopes enhanced virus clearance in vivo although they lacked virus neutralizing activity in vitro. To determine whether activating FcγR or complement were required for the antiviral effect of LCMV-specific Abs, mice deficient in the FcRγ chain or the complement component C3 were used. Similar to the findings described above with B6 mice, treatment of LCMV-infected FcRγ−/− or C3−/− mice with LCMV immune serum or the NP-specific mAb KL53 considerably lowered viral load in spleen, lungs, and liver compared with that in mice treated with normal serum (Fig. 9A and B). The overall reductions in viral titers by the Ab transfers were comparable in FcRγ−/−, C3−/−, and B6 wild-type mice (Fig. 9A and B versus Fig. 5 and 8). To exclude compensatory JNK inhibitor mechanisms between these two innate pathways, we repeated the anti-NP mAb transfer

experiments with mice deficient for both C3 and FcRγ. As shown in Fig. 9C, the transfer of LCMV NP specific Ab also accelerated LCMV clearance in FcRγ−/−C3−/− double-deficient mice. Moreover, transfer of LCMV NP specific mAb also decreased viral titers in LCMV-infected FcRγ−/−FcγRIIB−/− double-deficient mice indicating that FcγRIIB

was also dispensable for the antiviral activity of these Abs (Fig. 9D). Taken together, these data indicated that neither FcγR nor complement component C3 were required for the antiviral activity of the transferred LCMV NP-specific Abs. Here, we demonstrate in the LCMV infection model that the requirement for adaptive humoral immunity in addition to CD8+ T cells is strongly dependent on the replication speed of the viral strains used for inoculation. An adaptive Ab response Y-27632 2HCl was required to control infection with the rapidly replicating Docile strain but was dispensable for other strains with lower replication speed. To provide direct evidence that LCMV-specific Abs assisted virus elimination, Ab transfer experiments were performed. The experiments showed that IgG Abs isolated from LCMV immune serum possessed antiviral activity in vivo. These Abs were mainly directed against LCMV NP and completely lacked virus neutralizing activity. The antiviral activity of NP-specific Abs could be further demonstrated using mAbs with single antigen specificity. The mechanism by which LCMV NP specific Abs accelerate virus elimination is not yet known.