Induction of secreted human immunodeficiency virus type 1 (HIV-1) resistance factors in CD4-positive T lymphocytes by attenuated HIV-1 infection.
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.
Simm
Malgorzata
M
Molecular Virology Division, St. Luke's-Roosevelt Hospital Center, Antenucci Researech Building, 432 West 58th Street, New York, NY 10019, USA.
Miller
Lloyd S
LS
Durkin
Helen G
HG
Allen
Melrose
M
Chao
Wei
W
Lesner
Adam
A
Potash
Mary Jane
MJ
Volsky
David J
DJ
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
D004279:DNA, Viral; D016346:Gene Products, vif; D054320:vif Gene Products, Human Immunodeficiency Virus