Plasmodium sporozoites require the protein B9 to invade hepatocytes
Priyanka Fernandes,
Manon Loubens,
Carine Marinach,
Romain Coppée,
Ludivine Baron,
Morgane Grand,
Thanh-Phuc Andre,
Soumia Hamada,
Anne-Claire Langlois,
Sylvie Briquet,
Philippe Bun,
Olivier Silvie
Affiliations
Priyanka Fernandes
Sorbonne Université, INSERM, CNRS, Centre d’Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France
Manon Loubens
Sorbonne Université, INSERM, CNRS, Centre d’Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France
Carine Marinach
Sorbonne Université, INSERM, CNRS, Centre d’Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France
Romain Coppée
Université de Paris, UMR 261 MERIT, IRD, 75006 Paris, France
Ludivine Baron
Sorbonne Université, INSERM, CNRS, Centre d’Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France
Morgane Grand
Sorbonne Université, INSERM, CNRS, Centre d’Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France
Thanh-Phuc Andre
Sorbonne Université, INSERM, CNRS, Centre d’Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France
Soumia Hamada
Sorbonne Université, INSERM, CNRS, Centre d’Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France; Sorbonne Université, INSERM, UMS PASS, Plateforme Post-génomique de la Pitié Salpêtrière (P3S), 75013 Paris, France
Anne-Claire Langlois
Sorbonne Université, INSERM, CNRS, Centre d’Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France
Sylvie Briquet
Sorbonne Université, INSERM, CNRS, Centre d’Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France
Philippe Bun
INSERM U1266, NeurImag Facility, Institute of Psychiatry and Neurosciences of Paris, Paris, France
Olivier Silvie
Sorbonne Université, INSERM, CNRS, Centre d’Immunologie et des Maladies Infectieuses, CIMI-Paris, Paris, France; Corresponding author
Summary: Plasmodium sporozoites are transmitted to a mammalian host during blood feeding by an infected mosquito and invade hepatocytes for initial replication of the parasite into thousands of erythrocyte-invasive merozoites. Here we report that the B9 protein, a member of the 6-cysteine domain protein family, is secreted from sporozoite micronemes and is required for productive invasion of hepatocytes. The N-terminus of B9 forms a beta-propeller domain structurally related to CyRPA, a cysteine-rich protein forming an essential invasion complex in Plasmodium falciparum merozoites. The beta-propeller domain of B9 is essential for sporozoite infectivity and interacts with the 6-cysteine proteins P36 and P52 in a heterologous expression system. Our results suggest that, despite using distinct sets of parasite and host entry factors, Plasmodium sporozoites and merozoites may share common structural modules to assemble protein complexes for invasion of host cells.
