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Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases
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Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases

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Plasmodium parasitophorous vacuole membrane-resident protein UIS4 manipulates host cell actin to avoid parasite

Viriato M'Bana1,2, Aparajita Lahree1, Sofia Marques1

  • 1Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal.

Iscience
|May 16, 2022
PubMed

Insights

The Plasmodium sporozoite protein UIS4 interacts with host actin to suppress its formation, preventing parasite elimination. Inhibiting host myosin-II also impairs parasite clearance, highlighting UIS4's role in evading host defenses.

Area of Science:

  • Cellular and Molecular Biology
  • Parasitology
  • Immunology

Background:

  • Parasite-derived proteins residing at the PVM are crucial for parasite development within hepatocytes.
  • The specific functions of most PVM-resident proteins, including their roles in host-parasite interactions, remain largely uncharacterized.

Purpose of the Study:

  • To investigate the function of the PVM-resident protein UIS4 (upregulated in infectious sporozoites 4).
  • To determine the role of UIS4 in parasite survival and evasion of host immune responses within hepatocytes.

Main Methods:

  • Investigated the interaction between UIS4 and host cell actin.
  • Assessed the impact of UIS4 on filamentous actin formation and dynamics.
  • Examined the effect of inhibiting host myosin-II on parasite elimination.

Main Results:

  • UIS4 directly interacts with host cell actin, suppressing its polymerization.
  • UIS4 deficiency leads to increased host cell actin dynamics around parasites, resulting in parasite elimination.
  • Inhibition of host myosin-II significantly impairs parasite elimination, suggesting a role for actomyosin complexes in host defense.

Conclusions:

  • UIS4 plays a critical role in enabling the survival and development of the early-emergent form (EEF) of the parasite within hepatocytes.
  • UIS4 facilitates parasite evasion of host defensive mechanisms by modulating host actin dynamics.
  • Targeting host actomyosin pathways may represent a strategy to combat parasite infections.
Keywords:
cell biologymicrobial interactionsparasitology

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