Plasmodium berghei Dp52&p36 Parasites Develop Independent of a Parasitophorous Vacuole Membrane in Huh-7 Liver Cells

The proteins P52 and P36 are expressed in the sporozoite stage of the murine malaria parasite Plasmodium berghei. Dp52&p36 sporozoites lacking expression of both proteins are severely compromised in their capability to develop into liver stage parasites and abort development soon after invasion; presumably due to the absence of a parasitophorous vacuole membrane (PVM). However, a small proportion of P. berghei Dp52&p36 parasites is capable to fully mature in hepatocytes causing breakthrough blood stage infections. We have studied the maturation of replicating Dp52&p36 parasites in cultured Huh-7 hepatocytes. Approximately 50% of Dp52&p36 parasites developed inside the nucleus of the hepatocyte but did not complete maturation and failed to produce merosomes. In contrast cytosolic Dp52&p36 parasites were able to fully mature and produced infectious merozoites. These Dp52&p36 parasites developed into mature schizonts in the absence of an apparent parasitophorous vacuole membrane as shown by immunofluorescence and electron microscopy. Merozoites derived from these maturing Dp52&p36 liver stages were infectious for C57BL/6 mice. Citation: Ploemen IHJ, Croes HJ, van Gemert G-JJ, Wijers-Rouw M, Hermsen CC, et al. (2012) Plasmodium berghei Dp52&p36 Parasites Develop Independent of a Parasitophorous Vacuole Membrane in Huh-7 Liver Cells. PLoS ONE 7(12): e50772. doi:10.1371/journal.pone.0050772 Editor: Stefan Kappe, Seattle Biomedical Research Institute, University of Washington, United States of America Received July 16, 2012; Accepted October 24, 2012; Published December 5, 2012 Copyright: 2012 Ploemen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was performed within the framework of Top Institute Pharma (Netherlands) project: T4-102 (www.tipharma.com). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected]