<i>Plasmodium</i> Parasitophorous Vacuole Membrane-Resident Protein UIS4 Manipulates Host Cell Actin to Avoid Parasite Elimination

Abstract

Parasite-derived PVM-resident proteins are critical for complete parasite development inside hepatocytes (Hanson et al., 2013; Mueller et al., 2005), although the function of most of these proteins remains unknown. Here, we show that the Up-Regulated in Infectious Sporozoites 4 (UIS4) protein, resident at the PVM, interacts with the host-cell actin. By suppressing filamentous actin formation UIS4 avoids parasite elimination. Host-cell actin dynamics increases around UIS4-deficient parasites, which is associated with subsequent parasite elimination. Notably, parasite elimination is impaired significantly by the inhibition of host myosin-II, possibly through relieving the compression generated by actomyosin complexes at the host-parasite interface. Together, these data reveal that UIS4 has a critical role in the evasion of host defensive mechanisms, enabling hence EEF survival and development.