title: HIV-1 envelope-dependent restriction of CXCR4-using viruses in child but not adult untransformed CD4+ T-lymphocyte lines.
abstract: Phytohemagglutin-stimulated child and adult leukocytes equally supported CCR5-dependent (R5) and CXCR4-dependent (X4) HIV-1 replication. In contrast, when phytohemagglutin-stimulated leukocytes from either healthy or congenitally immunodeficient children were cultured on feeder cells, they well supported R5, but not X4 HIV-1 replication, whereas both viruses equally spread in adult cells maintained in similar conditions. Both child and adult cells showed similar levels of proliferation and surface expression of CD4, CCR5, CXCR4, CD25, CD69, and HLA-DR. Lack of X4 HIV-1 replication in child versus adult cells was not caused by a differential expression of several known HIV-1 restriction factors. Similar levels of HIV DNA synthesis occurred in child cells infected with R5 and X4 viruses up to 48 hours after infection when R5 HIV-1 showed a significantly superior capacity to spread in culture than X4 virus. Cultured child cells well supported single round vescicular stomatitis virus-G pseudotyped virus replication, whereas superinfection of R5-infected cells with X4 HIV-1 (or vice versa) rescued the replication of this latter virus. Thus, child cells exposed to feeder cell culture represent a novel model system in which the superior capacity of R5 versus X4 viruses to spread can be investigated in primary, untransformed CD4(+) cells.
authors.affiliation: AIDS Immunopathogenesis, San Raffaele Scientific Institute, Via Olgettina No. 58, Milan, Italy.
authors.forename: Samanta A
authors.initials: SA
authors.lastname: Mariani
authors.forename: Immacolata
authors.initials: I
authors.lastname: Brigida
authors.forename: Anna
authors.initials: A
authors.lastname: Kajaste-Rudnitski
authors.forename: Silvia
authors.initials: S
authors.lastname: Ghezzi
authors.forename: Alessia
authors.initials: A
authors.lastname: Rocchi
authors.forename: Anna
authors.initials: A
authors.lastname: Plebani
authors.forename: Elisa
authors.initials: E
authors.lastname: Vicenzi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Aiuti
authors.forename: Guido
authors.initials: G
authors.lastname: Poli
mesh_terms: D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002460:Cell Line; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D015316:Genetic Therapy; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007223:Infant; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D016511:Severe Combined Immunodeficiency / Q000276:immunology / Q000628:therapy; D014157:Transcription Factors / Q000378:metabolism; D014779:Virus Replication; D054299:env Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
chemical_list: D015704:CD4 Antigens; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014157:Transcription Factors; D054299:env Gene Products, Human Immunodeficiency Virus