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The Journal of Immunology, 2003, 170: 1566-1578.
Copyright © 2003 by The American Association of Immunologists

Induction of Apoptosis by HIV-1-Infected Monocytic Cells ¹

Kirk Sperber^2,*,, Prarthana Beuria^*,, Netai Singha, Irwin Gelman, Patricia Cortes, Houchu Chen^*, and Thomas Kraus

^* Division of Clinical Immunology, Immunobiology Institute, and Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029

We have previously described a soluble 6000-Da peptide produced by an HIV-1-infected human macrophage cell line, clone 43_HIV, which induces apoptosis in T and B cells. We have identified this factor as the novel cDNA clone FL14676485 that encodes for the human hypothetical protein, FLJ21908. The FL14676485 cDNA clone was isolated from a 43_HIV ZAP Escherichia coli expression library and screened with a panel of rabbit and mouse anti-apoptotic Abs. We transfected the FL14676485 clone into Bosc cells and non-HIV-1-infected 43 cells. Western blot analysis of lysates from the FL14676485-transfected 43 cells and Bosc cells using anti-proapoptotic factor Abs revealed a protein with a molecular mass of 66 kDa corresponding to the size of the full-length gene product of the FL14676485 clone, while Western blot of the supernatant demonstrated a doublet of 46-kDa and 6000-Da peptide that corresponds to our previously described proapoptotic factor. Primary HIV-1_BaL-infected monocytes also produce the FLJ21908 protein. Supernatants from these transfected cells induced apoptosis in PBMC, CD4⁺, and CD8⁺ T and B cells similar to the activity of our previously described proapoptotic factor. PCR analysis of 43 cells and 43_HIV cells revealed a base pair fragment of 420 bp corresponding to the FL14676485 gene product in 43_HIV cells, but not in 43 cells. The FLJ21908 protein induces apoptosis through activation of caspase-9 and caspase-3. We have further demonstrated that the FLJ21908 protein has apoptotic activity in the SH-SY5Y neuronal cell line and can be detected in brain and lymph tissue from HIV-1-infected patients who have AIDS dementia. The FLJ21908 protein may contribute to the apoptosis and dementia observed in AIDS patients.

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Retraction: Induction of Apoptosis by HIV-1-Infected Monocytic Cells

Kirk Sperber, Prarthana Beuria, Netai Singha, Irwin Gelman, Patricia Cortes, Houchu Chen, Netai Singha, Irwin Gelman, and Thomas Kraus
The JI 2005 175: 8438. [Full Text]  

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