Hepatocyte Permissiveness to Plasmodium Infection Is Conveyed by a Short and Structurally Conserved Region of the CD81 Large Extracellular Domain

摘要: Invasion of hepatocytes by Plasmodium sporozoites is a prerequisite for establishment malaria infection, and thus represents an attractive target anti-malarial interventions. Still, the molecular mechanisms underlying sporozoite invasion are largely unknown. We have previously reported that tetraspanin CD81, known receptor hepatitis C virus (HCV), required on infection several species. Here we characterized CD81 determinants hepatocytic cells P. yoelii sporozoites. Using CD9/CD81 chimeras, identified in 21 amino acid stretch located domain structurally conserved large extracellular loop tetraspanins, which sufficient otherwise CD9 background to confer susceptibility infection. By site-directed mutagenesis, demonstrated key role solvent-exposed region around residue D137 within this domain. A mAb requires optimal binding did not block contrast other mAbs. This study has uncovered new functionally important independent HCV E2 envelope protein domain, further suggests may interact directly with parasite ligand during but instead regulate function yet unknown partner protein.