FIG. 5.

PF4 oligomeric state correlates with its biphasic activity on viral infection. (A) MAGI-R5 cells were infected with HIV-1 pseudoviruses bearing the glycoprotein of MLV (top), JRFL (middle), and VSV (bottom) in the absence or increasing presence of PF4^WT, PF4^K50E, or PF4^E28R/K50E. (B) Virus entry was measured at high (4 μM) concentrations of PF4^WT, PF4^K50E, or PF4^E28R/K50E. PF4WT enhanced infection of HIV-1_JRFL and HIV-1_MLV approximately twofold. PF4^K50E significantly inhibited HIV-1_JRFL, HIV-1_MLV, and HIV-1_VSV-G entry. PF4^E28R/K50E restored the enhancement observed with PF4^WT. PF4^WT and PF4^E28R/K50E did not significantly impact HIV-1_VSV-G entry. (C) High concentrations of the monomer-favoring mutant PF4^K50E significantly reduced viral binding to cells. All experiments were done in at least triplicate in each of at least three independent experiments. Error bars represent standard deviations. ns, p > 0.05; *p < 0.05; **p < 0.005; ***p < 0.0001.