The Journal of Experimental Medicine
IN Cell Analyzer 2000
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© The Rockefeller University Press, 0022-1007/1999/5/1391/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 9, May 3, 1999 1391-1398

Articles

Expression of the c-myc Proto-oncogene Is Essential for HIV-1 Infection in Activated T Cells

Yu Sun* and Edward A. Clark*,{ddagger}

From the * Regional Primate Research Center and the {ddagger} Department of Microbiology, University of Washington, Seattle, Washington 98195

We previously found that activation of primary CD4+ T cells via both the T cell antigen receptor (TCR) and CD28 is required for HIV-1 DNA to be translocated from the cytoplasm to the nucleus. Here we report that expression of c-Myc protein in CD4+ T cells is induced only after such costimulation. In addition, cyclosporin A not only inhibits nuclear import of HIV-1 DNA but also inhibits expression of c-Myc protein. Because of these correlations, we tested whether c-Myc is necessary for nuclear import of HIV-1 DNA. Specific c-myc antisense, but not sense or non-sense, phosphorothioate oligodeoxynucleotides selectively induced the accumulation of two NH2-terminally truncated c-Myc proteins and abolished HIV-1 genome entry into host nuclei. Consequently, both virus replication and HIV-1–induced apoptotic cell death were inhibited. Synthesis of viral full-length DNA was not affected. Specific c-myc antisense oligonucleotide inhibited HIV-1 infection under conditions that did not affect cell cycle entry or proliferation. Thus, c-Myc appears to regulate HIV-1 DNA nuclear import via a mechanism distinct from those controlling entry into the cell cycle.

Key Words: c-Myc • HIV-1 DNA • T cell • nuclear import • apoptosis

Address correspondence to Edward A. Clark, Regional Primate Research Center, Box 357330, University of Washington, Seattle, WA 98195. Phone: 206-543-8706; Fax: 206-685-0305; E-mail: eclark{at}bart.rprc.washington.edu

Abbreviations used: c-MycS, c-Myc short; CSA, cyclosporin A; PS-ODN, phosphorothioate oligodeoxynucleotide; PIC, pre-integration complexes; TUNEL, TdT-mediated dUTP nick-end labeling.


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