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We previously reported that the <jats:italic>Rvfs2<\/jats:italic> locus from the susceptible MBT\/Pas strain reduces survival time after RVFV infection. Here, we used BALB\/cByJ (BALB) mice congenic for <jats:italic>Rvfs2<\/jats:italic> (C.MBT-<jats:italic>Rvfs2<\/jats:italic>) to investigate the pathophysiological mechanisms impacted by <jats:italic>Rvfs2<\/jats:italic>. Clinical, biochemical and histopathological features indicated similar liver damage in BALB and C.MBT-<jats:italic>Rvfs2<\/jats:italic> mice until day 5 after infection. However, while C.MBT-<jats:italic>Rvfs2<\/jats:italic> mice succumbed from acute liver injury, most BALB mice recovered and died later of encephalitis. Hepatocytes of BALB infected liver proliferated actively on day 6, promoting organ regeneration and recovery from liver damage. By comparison with C.MBT-<jats:italic>Rvfs2<\/jats:italic>, BALB mice had up to 100-fold lower production of infectious virions in the peripheral blood and liver, strongly decreased RVFV protein in liver and reduced viral replication in primary cultured hepatocytes, suggesting that the BALB <jats:italic>Rvfs2<\/jats:italic> haplotype limits RVFV pathogenicity through decreased virus replication. Moreover, bone marrow chimera experiments showed that both hematopoietic and non-hematopoietic cells are required for the protective effect of the BALB <jats:italic>Rvfs2<\/jats:italic> haplotype. Altogether, these results indicate that <jats:italic>Rvfs2<\/jats:italic> controls critical events which allow survival to RVFV-induced hepatitis.<\/jats:p>","DOI":"10.1038\/s41598-020-65683-w","type":"journal-article","created":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T10:02:38Z","timestamp":1590487358000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Genetic dissection of Rift Valley fever pathogenesis: Rvfs2 locus on mouse chromosome 11 enables survival to early-onset hepatitis"],"prefix":"10.1038","volume":"10","author":[{"given":"Leandro","family":"Batista","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0188-2554","authenticated-orcid":false,"given":"Gregory","family":"Jouvion","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Simon-Chazottes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Houzelstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Odile","family":"Burlen-Defranoux","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magali","family":"Boissi\u00e8re","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoko","family":"Tokuda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania Zaverucha","family":"do Valle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Cumano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Flamand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9372-5398","authenticated-orcid":false,"given":"Xavier","family":"Montagutelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Jacques","family":"Panthier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,5,26]]},"reference":[{"key":"65683_CR1","unstructured":"WHO. 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