PMID- 10224279 OWN - NLM STAT- MEDLINE DCOM- 19990615 LR - 20190508 IS - 0022-1007 (Print) IS - 0022-1007 (Linking) VI - 189 IP - 9 DP - 1999 May 3 TI - Expression of the c-myc proto-oncogene is essential for HIV-1 infection in activated T cells. PG - 1391-8 AB - 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. FAU - Sun, Y AU - Sun Y AD - Regional Primate Research Center, University of Washington, Seattle, Washington 98195, USA. FAU - Clark, E A AU - Clark EA LA - eng GR - P51 RR000166/RR/NCRR NIH HHS/United States GR - RR00166/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Exp Med JT - The Journal of experimental medicine JID - 2985109R RN - 0 (DNA, Viral) RN - 0 (Proto-Oncogene Proteins c-myc) SB - IM SB - X MH - CD4-Positive T-Lymphocytes/metabolism/*virology MH - Cells, Cultured MH - DNA, Viral/metabolism MH - Gene Expression MH - HIV-1/genetics/metabolism/*physiology MH - Humans MH - Lymphocyte Activation MH - Proto-Oncogene Proteins c-myc/genetics/*metabolism PMC - PMC2193066 EDAT- 1999/05/04 00:00 MHDA- 1999/05/04 00:01 CRDT- 1999/05/04 00:00 PHST- 1999/05/04 00:00 [pubmed] PHST- 1999/05/04 00:01 [medline] PHST- 1999/05/04 00:00 [entrez] AID - 10.1084/jem.189.9.1391 [doi] PST - ppublish SO - J Exp Med. 1999 May 3;189(9):1391-8. doi: 10.1084/jem.189.9.1391.