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CD8⁺ cell noncytotoxic anti-human immunodeficiency virus response inhibits expression of viral RNA but not reverse transcription or provirus integration

Department of Medicine, Box 1270, University of California, San Francisco, CA 94143, USA¹
Children’s Memorial Hospital, Chicago, IL, USA²

Author for correspondence: Jay Levy. Fax +1 415 476 8365.

CD8⁺ T cells from human immunodeficiency virus (HIV)-infected individuals can suppress HIV replication in CD4⁺ cells by a noncytotoxic mechanism that inhibits the expression of viral RNA. The present study examined whether other step(s) in the virus replicative cycle could be affected by the CD8⁺ cells. Culturing HIV-infected CD4⁺ T cells with antiviral CD8⁺ T cells did not significantly reduce the amounts of (i) early HIV DNA reverse transcripts (detected by LTR-U3/R), (ii) total nuclear HIV gag DNA, or (iii) integrated proviral DNA. However, exposure to the CD8⁺ T cells did cause a reduction in the amount of multiply spliced tat and full-length gag mRNA expressed by the infected CD4⁺ T cells, confirming previous observations. The levels of glyceraldehyde-3-phosphate dehydrogenase and interleukin-2 receptor- mRNA were not affected. The results support the conclusion that the noncytotoxic anti-HIV response of CD8⁺ T cells, demonstrable in vitro, does not affect any of the virus replication steps leading to the integration of proviral HIV, but specifically interrupts the expression of viral RNA.

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