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After reaching the liver by the blood stream, <jats:italic>Plasmodium<\/jats:italic> sporozoites cross the liver sinusoid epithelium, enter and exit several hepatocytes, and eventually invade a final hepatocyte host cell. At present, the mechanism of hepatocyte invasion is only partially understood, presenting a key research gap with opportunities for the development of new therapeutics. Recently, human EphA2, a membrane-bound receptor tyrosine kinase, was implicated in hepatocyte infection by the human malaria parasite <jats:italic>Plasmodium falciparum<\/jats:italic> and the rodent parasite <jats:italic>Plasmodium yoelii<\/jats:italic>, but its role is not known for <jats:italic>Plasmodium vivax<\/jats:italic>, a major human parasite whose liver infection poses a specific challenge for malaria treatment and elimination. In this study, the role of EphA2 in <jats:italic>P. vivax<\/jats:italic> infection was investigated. It was found that surface expression of several recombinant fragments of EphA2 enhanced the parasite infection rate, thus establishing its role in <jats:italic>P. vivax<\/jats:italic> infection. Furthermore, a new permanent cell line (EphA2Extra-HC04) expressing the whole extracellular domain of EphA2 was generated. This cell line supports a higher rate of <jats:italic>P. vivax<\/jats:italic> infection and is a valuable tool for <jats:italic>P. vivax<\/jats:italic> liver-stage research.<\/jats:p>","DOI":"10.1038\/s41598-022-25281-4","type":"journal-article","created":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T13:03:44Z","timestamp":1670936624000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Overexpression of hepatocyte EphA2 enhances liver-stage infection by Plasmodium vivax"],"prefix":"10.1038","volume":"12","author":[{"given":"Sittinont","family":"Chainarin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ubonwan","family":"Jaihan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parsakorn","family":"Tapaopong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pinyapat","family":"Kongngen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nawapol","family":"Kunkeaw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liwang","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jetsumon","family":"Sattabongkot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wang","family":"Nguitragool","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanlapa","family":"Roobsoong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"25281_CR1","doi-asserted-by":"publisher","first-page":"E4","DOI":"10.1371\/journal.pbio.0020004","volume":"2","author":"T Ishino","year":"2004","unstructured":"Ishino, T., Yano, K., Chinzei, Y. & Yuda, M. Cell-passage activity is required for the malarial parasite to cross the liver sinusoidal cell layer. PLoS Biol. 2, E4. https:\/\/doi.org\/10.1371\/journal.pbio.0020004 (2004).","journal-title":"PLoS Biol."},{"key":"25281_CR2","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1111\/j.1462-5822.2004.00447.x","volume":"7","author":"T Ishino","year":"2005","unstructured":"Ishino, T., Chinzei, Y. & Yuda, M. A Plasmodium sporozoite protein with a membrane attack complex domain is required for breaching the liver sinusoidal cell layer prior to hepatocyte infection. Cell. Microbiol. 7, 199\u2013208. https:\/\/doi.org\/10.1111\/j.1462-5822.2004.00447.x (2005).","journal-title":"Cell. Microbiol."},{"key":"25281_CR3","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1084\/jem.20121130","volume":"210","author":"J Tavares","year":"2013","unstructured":"Tavares, J. et al. Role of host cell traversal by the malaria sporozoite during liver infection. J. Exp. 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