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.