title: Infection of simian B lymphoblastoid cells with simian immunodeficiency virus is associated with upregulation of CD23 and CD40 cell surface markers.
abstract: Simian immunodeficiency virus (SIV) as well as human immunodeficiency virus (HIV) induce polyclonal B-cell activation and are associated with the appearance of lymphomas in their respective hosts in either the presence or the absence of other co-infecting viruses such as Epstein-Barr virus (EBV). However, the pathogenic role of these retroviruses in the development of lymphoproliferative disorders remains poorly understood. To explore the virus-B-cell interactions, two immortalized lymphoblastoid B-cell lines (SL-P1 and SL-691) were established from cynomolgus monkeys that were naturally co-infected with a simian type D retrovirus-2 (SRV-2) and with the herpes virus Macaca fascicularis (HVMF-1). We addressed their susceptibility to SIV infection and the phenotypic modifications associated with SIV infection. In response, both cell lines (1) were co-infected with HVMF-1 (latent infection) and with SRV-2 (productive infection), (2) had a transformed phenotype because they did not require exogenous growth factors, and (3) when injected into mice with severe combined immunodeficiency (SCID), generated serially transplantable tumors. The B-cell origin of SL cells was demonstrated by the presence of rearrangements of the IgH gene and by the expression of typical B-cell lineage markers, such as CD20. SL-P1 and SL-691 could be discriminated on the basis of different expressions of CD23 and CD40 and of kappa- and lambda-chains. Most importantly, SL-691 cells, but not SL-P1 cells, were susceptible to chronic noncytolytic SIV infection. This infection occurred in a CD4/CCR5/CXCR4-independent manner and was associated with the upregulated expression of CD23 and CD40 cell surface markers. In addition, CD20 expression, which progressively disappeared in SL-691 noninfected cells, was maintained in the SIV-infected counterpart. These findings support the hypothesis that SIV induce phenotypic perturbations in B cells that might eventually contribute to the development of lymphoproliferative disease.
authors.affiliation: Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy. titti@iss.it
authors.forename: Fausto
authors.initials: F
authors.lastname: Titti
authors.forename: Rita
authors.initials: R
authors.lastname: Zamarchi
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Maggiorella
authors.forename: Leonardo
authors.initials: L
authors.lastname: Sernicola
authors.forename: Andrea
authors.initials: A
authors.lastname: Geraci
authors.forename: Donatella Rita Maria
authors.initials: DR
authors.lastname: Negri
authors.forename: Alessandra
authors.initials: A
authors.lastname: Borsetti
authors.forename: Chiara
authors.initials: C
authors.lastname: Menin
authors.forename: Emma
authors.initials: E
authors.lastname: D'Andrea
authors.forename: Andrea
authors.initials: A
authors.lastname: Modesti
authors.forename: Laura
authors.initials: L
authors.lastname: Masuelli
authors.forename: Paola
authors.initials: P
authors.lastname: Verani
authors.forename: Luigi
authors.initials: L
authors.lastname: Chieco-Bianchi
authors.forename: Alberto
authors.initials: A
authors.lastname: Amadori
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D030121:Betaretrovirus / Q000235:genetics; D015415:Biomarkers; D019013:CD40 Antigens / Q000276:immunology*; D019070:Cell Lineage; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D016679:Genome, Viral; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000821:virology; D006568:Herpesvirus 1, Cercopithecine / Q000235:genetics; D008252:Macaca fascicularis; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D017455:Receptors, IgE / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D019013:CD40 Antigens; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D017455:Receptors, IgE