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It has previously been shown that<jats:italic>L<\/jats:italic>.<jats:italic>guyanensis<\/jats:italic>strains that carry the endosymbiotic<jats:italic>Leishmania RNA virus 1<\/jats:italic>(LRV1) cause more severe form of the disease in a mouse model than those that do not. The presence of the virus was implicated into the parasite\u2019s replication and spreading. In this respect, studying the molecular mechanisms of cellular control of viral infection is of great medical importance. Here, we report ~30.5 Mb high-quality genome assembly of the LRV1-positive<jats:italic>L<\/jats:italic>.<jats:italic>guyanensis<\/jats:italic>M4147. This strain was turned into a model by establishing the CRISPR-Cas9 system and ablating the gene encoding phosphatidate phosphatase 2-like (PAP2L) protein. The orthologue of this gene is conspicuously absent from the genome of an unusual member of the family Trypanosomatidae,<jats:italic>Vickermania ingenoplastis<\/jats:italic>, a species with mostly bi-flagellated cells. Our analysis of the PAP2L-null<jats:italic>L<\/jats:italic>.<jats:italic>guyanensis<\/jats:italic>showed an increase in the number of cells strikingly resembling the bi-flagellated<jats:italic>V<\/jats:italic>.<jats:italic>ingenoplastis<\/jats:italic>, likely as a result of the disruption of the cell cycle, significant accumulation of phosphatidic acid, and increased virulence compared to the wild type cells.<\/jats:p>","DOI":"10.1371\/journal.pntd.0010510","type":"journal-article","created":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T18:03:39Z","timestamp":1656093819000},"page":"e0010510","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":17,"title":["Leishmania guyanensis M4147 as a new LRV1-bearing model parasite: Phosphatidate phosphatase 2-like protein controls cell cycle progression and intracellular lipid content"],"prefix":"10.1371","volume":"16","author":[{"given":"Alexandra","family":"Zakharova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda T. 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