{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T07:40:27Z","timestamp":1789371627941,"version":"build-2803163510"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2013,6,1]],"date-time":"2013-06-01T00:00:00Z","timestamp":1370044800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Rift Valley fever virus (RVFV) causes outbreaks of severe disease in people and livestock throughout Africa and the Arabian Peninsula. Human RVFV infections generally manifest as a self-limiting febrile illness, but in some individuals, the disease can progress to a fatal encephalitis or hemorrhagic syndrome. Little is known about the host characteristics that predispose development of more severe disease. Early in infection, interferon-mediated antiviral responses are critical for controlling RVFV replication, but the roles of downstream adaptive immune responses in determining clinical outcome have not been examined. Here, using a C57BL\/6 mouse disease model, we evaluated the roles of B cells and T cells in RVFV pathogenesis. Given the profound inhibition of the innate response by the viral NSs protein and rapid course of wild-type infection, we utilized an attenuated RVFV lacking NSs to examine host responses following primary infection. Experiments utilizing B-cell-deficient mice or targeted T cell depletions of wild-type mice demonstrated that B cells and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells, but not CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, were critical for mediating viral clearance, even in the presence of a functional innate response. One-third of CD4-depleted mice developed severe neurologic disease following infection, in contrast to virus-infected mock-depleted mice that showed no clinical signs. CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells were required for robust IgG and neutralizing antibody responses that correlated with RVFV clearance from peripheral tissues. Furthermore, CD4-depleted mice demonstrated significantly stronger proinflammatory responses relative to controls, suggesting CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells regulate immune responses to RVFV infection. Together, these results indicate CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells are critical determinants of RVFV pathogenesis and play an important role in preventing onset of neurologic disease.\n                  <\/jats:p>","DOI":"10.1128\/jvi.00337-13","type":"journal-article","created":{"date-parts":[[2013,3,27]],"date-time":"2013-03-27T21:54:33Z","timestamp":1364421273000},"page":"6161-6171","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":57,"title":["Rift Valley Fever Virus Clearance and Protection from Neurologic Disease Are Dependent on CD4\n                    <sup>+<\/sup>\n                    T Cell and Virus-Specific Antibody Responses"],"prefix":"10.1128","volume":"87","author":[{"given":"Kimberly A.","family":"Dodd","sequence":"first","affiliation":[{"name":"Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA"},{"name":"University of California, Davis, School of Veterinary Medicine, Davis, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita K.","family":"McElroy","sequence":"additional","affiliation":[{"name":"Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA"},{"name":"Emory University School of Medicine, Department of Pediatrics, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan E. B.","family":"Jones","sequence":"additional","affiliation":[{"name":"Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA"},{"name":"Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart T.","family":"Nichol","sequence":"additional","affiliation":[{"name":"Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina F.","family":"Spiropoulou","sequence":"additional","affiliation":[{"name":"Viral Special Pathogens Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","unstructured":"ChevalierV\nP\u00e9pinM\nPl\u00e9eL\nLancelotR. 2010. Rift Valley fever\u2014a threat for Europe? Euro Surveill. 15:19506. http:\/\/www.eurosurveillance.org\/ViewArticle.aspx?ArticleId=19506.","DOI":"10.2807\/ese.15.10.19506-en"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2009.02849.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jmedent\/47.5.884"},{"key":"e_1_3_2_5_2","first-page":"423","volume-title":"Oxford textbook of zoonoses: biology, clinical practice, and public health","author":"Swanepoel R","year":"2011","unstructured":"SwanepoelR PaweskaJT. 2011. Rift Valley fever, p 423\u2013431. In PalmerS SoulsbyL TorgersonP BrownDWG (ed), Oxford textbook of zoonoses: biology, clinical practice, and public health, 2nd ed. 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