{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T07:33:22Z","timestamp":1772782402328,"version":"3.50.1"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T00:00:00Z","timestamp":1659657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p><jats:italic>Neospora caninum<\/jats:italic>represents a major cause of abortive disease in bovines and small ruminants worldwide. As a typical obligate intracellular apicomplexan parasite,<jats:italic>N. caninum<\/jats:italic>needs to modulate its host cell for successful replication. In the current study, we focused on parasite-driven interference with host cell cycle progression. By performing DNA content-based cell cycle phase analyses in<jats:italic>N. caninum<\/jats:italic>-infected primary bovine umbilical vein endothelial cells (BUVEC), a parasite-driven S-phase arrest was detected at both 24 and 32\u00a0h p. i., being paralleled by fewer host cells experiencing the G0\/G1 cell cycle phase. When analyzing S-subphases, proliferation cell nuclear antigen (per PCNA)-based experiments showed a reduced population of BUVEC in the late S-phase. Analyses on key molecules of cell cycle regulation documented a significant alteration of cyclin A2 and cyclin B1 abundance in<jats:italic>N. caninum<\/jats:italic>-infected host endothelial cells, thereby confirming irregularities in the S-phase and S-to-G2\/M-phase transition. In line with cell cycle alterations, general nuclear parameters revealed smaller nuclear sizes and morphological abnormalities of BUVEC nuclei within the<jats:italic>N. caninum<\/jats:italic>-infected host cell layer. The latter observations were also confirmed by transmission electron microscopy (TEM) and by analyses of lamin B1 as a marker of nuclear lamina, which illustrated an inhomogeneous nuclear lamin B1 distribution, nuclear foldings, and invaginations, thereby reflecting nuclear misshaping. Interestingly, the latter finding applied to both non-infected and infected host cells within parasitized BUVEC layer. Additionally, actin detection indicated alterations in the perinuclear actin cap formation since typical nucleo-transversal filaments were consistently lacking in<jats:italic>N. caninum<\/jats:italic>-infected BUVEC, as also documented by significantly decreased actin-related intensities in the perinuclear region. These data indicate that<jats:italic>N. caninum<\/jats:italic>indeed alters host cell cycle progression and severely affects the host cell nuclear phenotype in primary bovine endothelial host cells. In summary, these findings add novel data on the complex<jats:italic>N. caninum<\/jats:italic>-specific modulation of host cell and nucleus, thereby demonstrating clear differences in cell cycle progression modulation driven by other closely related apicomplexans like<jats:italic>Toxoplasma gondii<\/jats:italic>and<jats:italic>Besnotia besnoiti<\/jats:italic>.<\/jats:p>","DOI":"10.3389\/fcell.2022.946335","type":"journal-article","created":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T11:10:04Z","timestamp":1659697804000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Neospora caninum Infection Triggers S-phase Arrest and Alters Nuclear Characteristics in Primary Bovine Endothelial Host Cells"],"prefix":"10.3389","volume":"10","author":[{"given":"Zahady D.","family":"Vel\u00e1squez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisbeth","family":"Rojas-Bar\u00f3n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camilo","family":"Larrazabal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo","family":"Salierno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"G\u00e4rtner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Learta","family":"Pervizaj-Oruqaj","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Herold","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Hermosilla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Taubert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,5]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.2460\/javma.1993.202.01.113","article-title":"Congenital Neospora Infection in Calves Born from Cows that Had Previously Aborted Neospora-Infected Fetuses: Four Cases (1990-1992)","volume":"202","author":"Barr","year":"1993","journal-title":"J. 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