{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:14:42Z","timestamp":1791274482765,"version":"4.1.0"},"reference-count":74,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001409","name":"Department of Science and Technology, Ministry of Science and Technology, India","doi-asserted-by":"crossref","award":["CRG\/2022\/005632\/BHS"],"award-info":[{"award-number":["CRG\/2022\/005632\/BHS"]}],"id":[{"id":"10.13039\/501100001409","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,11,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Apicomplexan parasites possess unique secretory organelles called rhoptries, which are reservoirs for rhoptry neck proteins (RONs) and rhoptry bulb proteins (ROPs) that aid in host cell attachment, invasion, and intracellular proliferation. In\n                      <jats:italic toggle=\"yes\">Plasmodium falciparum<\/jats:italic>\n                      , the RON6 (\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      RON6) locus is indispensable, limiting its functional investigation. Using a rodent malaria model, we show the role of\n                      <jats:italic toggle=\"yes\">P. berghei<\/jats:italic>\n                      RON6 (PbRON6), a putative ortholog of\n                      <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                      RON6, in the invasion of RBC, hepatocytes, and during liver stage development.\n                      <jats:italic toggle=\"yes\">Pb<\/jats:italic>\n                      RON6 localizes to the sporozoite membrane and has an extracellular C-terminal domain. RON6-depleted parasites fail to maintain infectivity and virulence, leading to prolonged survival of mice. The mutants induce chronic malaria and hyper-reactive malarial splenomegaly, characterized by decreased B and T lymphocytes concurring with loss of lymphoid follicles. Our findings provide a rationale for targeting\n                      <jats:italic toggle=\"yes\">Pb<\/jats:italic>\n                      RON6 in pre-erythrocytic stages to prevent clinical malaria and also for understanding the basis of hyper-reactive splenomegaly in mice using the\n                      <jats:italic toggle=\"yes\">Pb\u0394ron6<\/jats:italic>\n                      mutant model.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Plasmodium<\/jats:italic>\n                        sporozoites are infective to mammalian hepatocytes. Prior to entry into the cell, sporozoites release proteins from their apical cell organelles called micronemes and rhoptries. The secreted proteins contact the hepatocyte membrane to create a structure called a moving junction (MJ) that progressively invaginates inside the cell, utilizing the parasite\u2019s actomyosin molecular motor. This activity finally culminates in establishing an intracellular vacuole that harbors the parasite. As MJ is crucial for intracellular infection, targeting the components of this complex has implications in reducing malaria infection. We show that a rhoptry resident protein, RON6, is required for the invasion of merozoites and sporozoites, together with a role in the development of parasites in the hepatocytes. Consistent with its probable role in hepatocyte invasion, the RON6 is localized to the sporozoite membrane, with its C-terminal domain being extracellular. Our observations reveal that RON6 maintains the virulence of the parasite, and mutants lacking RON6 enhance host survival and induce hyper-reactive malarial splenomegaly.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01941-25","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T12:06:52Z","timestamp":1758802012000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["<i>Plasmodium berghei<\/i>\n                    rhoptry neck protein 6 maintains parasite infectivity and virulence"],"prefix":"10.1128","volume":"16","author":[{"given":"Veeda","family":"Narahari","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04a7rxb17","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Animal Biology, School of Life Sciences, University of Hyderabad","place":["Hyderabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smita","family":"Patri","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04a7rxb17","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Animal Biology, School of Life Sciences, University of Hyderabad","place":["Hyderabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minal Dilip","family":"Satpute","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04a7rxb17","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Animal Biology, School of Life Sciences, University of Hyderabad","place":["Hyderabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geeta Kashyap","family":"Vemuganti","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04a7rxb17","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Medical Sciences, University of Hyderabad","place":["Hyderabad, India"]},{"name":"L V Prasad Eye Institute","place":["Hyderabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilip Kumar","family":"Mishra","sequence":"additional","affiliation":[{"name":"L V Prasad Eye Institute","place":["Hyderabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6125-0036","authenticated-orcid":true,"given":"Surendra Kumar","family":"Kolli","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04a7rxb17","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Animal Biology, School of Life Sciences, University of Hyderabad","place":["Hyderabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9451-2917","authenticated-orcid":true,"given":"Kota","family":"Arun Kumar","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04a7rxb17","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Animal Biology, School of Life Sciences, University of Hyderabad","place":["Hyderabad, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","unstructured":"WHO. 2023. 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