title: Induction of secreted human immunodeficiency virus type 1 (HIV-1) resistance factors in CD4-positive T lymphocytes by attenuated HIV-1 infection.
abstract: This report describes induction of HIV-1 resistance and synthesis of resistance factors in immortal CD4-positive T lymphocytes. SupT1 cells were infected by NL4-3 attenuated by a defect in the vif gene through coculture with infected primary lymphocytes. Cell lines from this infection, termed R1, expressed CD4 and CXCR4, carried low levels of HIV-1 DNA, but expressed no other detectable viral products and were resistant to infection by wild-type HIV-1. Investigation of challenge infection in resistant R1 lines demonstrated entry, reverse transcription, and integration by incoming HIV-1 but no synthesis of viral RNA. By assay of marker gene expression, we found that Tat was unable to activate LTR-driven transcription in R1 lines. HIV-1-resistant R1 lines secreted soluble factors that inhibited productive infection of primary lymphocytes by several strains of HIV-1 and blocked viral RNA synthesis in newly infected cells. Resistance factors also blocked the induction of HIV-1 transcription in ACH-2 cells as assayed by viral antigen expression and Northern blot of viral RNA. Soluble factors produced by HIV-1-resistant, immortal R1 cells may form the basis of new approaches to control HIV-1 infection.
authors.affiliation: Molecular Virology Division, St. Luke's-Roosevelt Hospital Center, Antenucci Researech Building, 432 West 58th Street, New York, NY 10019, USA.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Simm
authors.forename: Lloyd S
authors.initials: LS
authors.lastname: Miller
authors.forename: Helen G
authors.initials: HG
authors.lastname: Durkin
authors.forename: Melrose
authors.initials: M
authors.lastname: Allen
authors.forename: Wei
authors.initials: W
authors.lastname: Chao
authors.forename: Adam
authors.initials: A
authors.lastname: Lesner
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Potash
authors.forename: David J
authors.initials: DJ
authors.lastname: Volsky
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D002461:Cell Line, Transformed; D004279:DNA, Viral / Q000378:metabolism; D016346:Gene Products, vif / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D014158:Transcription, Genetic; D016662:Virus Integration; D017735:Virus Latency; D014779:Virus Replication; D054320:vif Gene Products, Human Immunodeficiency Virus
chemical_list: D004279:DNA, Viral; D016346:Gene Products, vif; D054320:vif Gene Products, Human Immunodeficiency Virus