Human CD4+ cells transfected with IL-16 cDNA are resistant to HIV-1 infection: inhibition of mRNA expression.
Interleukin-16 (IL-16) is secreted by activated CD8+ T lymphocytes and acts on CD4+ T lymphocytes, monocytes and eosinophils. Recently, the C-terminal 130-amino acid portion of IL-16 was shown to suppress HIV-1 replication in vitro. To explore the potential of human IL-16 for gene therapy, this portion was transfected into HIV-1-susceptible CD4+ jurkat cells by means of a mammalian expression vector. The stable transfectants synthesized and secreted IL-16 protein. The expression of IL-16 did not alter growth rate and CD4 expression; however, HIV replication was inhibited by as much as 99%. Furthermore, during the initial phase of the infection, equal amounts of HIV-1 proviral DNA were found in cells transfected with IL-16 and with vector alone. In contrast, the 2-kilobase HIV-1 transcripts were markedly reduced and the 4-kb and 9-kb transcripts were undetectable in the cells transfected with IL-16. These findings indicate that IL-16-mediated inhibition of HIV-1 is not at the level of viral entry or reverse transcription, but at messenger RNA expression.
Zhou
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P
Branch of Oral Infection and Immunity, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Goldstein
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S
Devadas
K
K
Tewari
D
D
Notkins
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AL
D015152:Blotting, Northern; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D015726:Giant Cells / Q000187:drug effects; D016655:HIV Core Protein p24 / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D019410:Interleukin-16 / Q000378:metabolism*; D019169:Jurkat Cells; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014779:Virus Replication
D015704:CD4 Antigens; D004279:DNA, Viral; D016655:HIV Core Protein p24; D019410:Interleukin-16; D012333:RNA, Messenger