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It has been demonstrated previously that HIV-1 particles acquire the costimulatory molecule CD40L when budding from activated CD4<jats:sup>+<\/jats:sup>T cells. In this paper, we confirmed first that CD40L-bearing virions are detected in the plasma from untreated HIV-1-infected individuals. To define the biological functions of virus-associated CD40L and fully characterize its influence on the activation state of B cells, we conducted a large-scale gene expression analysis using microarray technology on B cells isolated from human tonsillar tissue. Comparative analyses of gene expression profiles revealed that CD40L-bearing virions induce a highly similar response to the one observed in samples treated with a CD40 agonist, indicating that virions bearing CD40L can efficiently activate B cells. Among modulated genes, many cytokines\/chemokines (CCL17, CCL22), surface molecules (CD23, CD80, ICAM-1), members of the TNF superfamily (FAS, A20, TNIP1, CD40, lymphotoxin alpha, lymphotoxin beta), transcription factors and associated proteins (NFKB1, NFKBIA, NFKBIE), second messengers involved in CD40 signaling (TRAF1, TRAF3, MAP2K1, phosphatidylinositol 3-kinase), and the activation-induced cytidine deaminase (AID) were identified. Moreover, we show that soluble factors induced upon the exposure of B cells to CD40L-bearing virions can exert chemoattractant properties toward CD4<jats:sup>+<\/jats:sup>T cells. We thus propose that a positive feedback loop involving CD40L-bearing HIV-1 particles issued from CD4<jats:sup>+<\/jats:sup>T cells productively infected with HIV-1 play a role in the virus-induced dysfunction of humoral immunity by chronically activating B cells through sustained CD40 signaling.<\/jats:p>","DOI":"10.1128\/jvi.01993-10","type":"journal-article","created":{"date-parts":[[2010,12,23]],"date-time":"2010-12-23T03:19:51Z","timestamp":1293074391000},"page":"2189-2200","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":46,"title":["Acquisition of Host-Derived CD40L by HIV-1<i>In Vivo<\/i>and Its Functional Consequences in the B-Cell Compartment"],"prefix":"10.1128","volume":"85","author":[{"given":"Michae\u0308l","family":"Imbeault","sequence":"first","affiliation":[{"name":"Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Que\u0301bec-CHUL, and De\u0301partement de Microbiologie-Infectiologie et Immunologie, Faculte\u0301 de Me\u0301decine, Universite\u0301 Laval, Que\u0301bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Ouellet","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Que\u0301bec-CHUL, and De\u0301partement de Microbiologie-Infectiologie et Immunologie, Faculte\u0301 de Me\u0301decine, Universite\u0301 Laval, Que\u0301bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Gigue\u0300re","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Que\u0301bec-CHUL, and De\u0301partement de Microbiologie-Infectiologie et Immunologie, Faculte\u0301 de Me\u0301decine, Universite\u0301 Laval, Que\u0301bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Bertin","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Que\u0301bec-CHUL, and De\u0301partement de Microbiologie-Infectiologie et Immunologie, Faculte\u0301 de Me\u0301decine, Universite\u0301 Laval, Que\u0301bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dave","family":"Be\u0301langer","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Que\u0301bec-CHUL, and De\u0301partement de Microbiologie-Infectiologie et Immunologie, Faculte\u0301 de Me\u0301decine, Universite\u0301 Laval, Que\u0301bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevie\u0300ve","family":"Martin","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Que\u0301bec-CHUL, and De\u0301partement de Microbiologie-Infectiologie et Immunologie, Faculte\u0301 de Me\u0301decine, Universite\u0301 Laval, Que\u0301bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel J.","family":"Tremblay","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Que\u0301bec-CHUL, and De\u0301partement de Microbiologie-Infectiologie et Immunologie, Faculte\u0301 de Me\u0301decine, Universite\u0301 Laval, Que\u0301bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.59.2.284-291.1986"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202568"},{"key":"e_1_3_3_4_2","first-page":"400","volume":"14","year":"1993","unstructured":"Berek, C., and M. 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