All of the results above were obtained with soluble forms of the E protein. In order to test the ability of exogenous pr peptide to interact with and inhibit intact DENV, we took advantage of a previously described assay that monitors low pH-triggered fusion of DENV with cells [41] . In this fusion-infection assay, virus is prebound to target cells on ice, and then treated at 37uC for 1 min at low pH to trigger virus fusion with the plasma membrane. This fusion reaction is then quantitated by detecting the infected cells by immunofluorescence. We tested the effect of pr peptide during this 1 min low pH treatment using DENV1 WP and DENV2 NGC. The sequence of E DI/II is 68% identical between these two serotypes. Both serotypes showed efficient fusion and infection after treatment at pH 6.0, with about a 10-fold increase compared to samples treated at pH 7.9 (Fig. 4 ). The addition of pr peptide during the 1 min low pH treatment strongly inhibited DENV fusion and infection. Inhibition was dose-dependent, with 45-49% inhibition at 6 mM pr and 81-85-% inhibition at 30 mM pr. In contrast, pr did not inhibit low pH-triggered fusion by the alphavirus SIN (Fig. 4) . Thus, exogenous DENV2 pr peptide can specifically interact with mature DENV1 and DENV2 to block virus fusion and infection. We did not observe inhibition when DENV was preincubated with 30 mM pr at pH 7.0 and then added to target cells in a standard infection assay, suggesting that under these conditions an inhibitory concentration of pr was not present during low pH-triggered fusion reaction in the endosome. This result also indicates that the presence of pr did not affect virus-cell binding.