Abstract
We investigated whether the high mobility group B 1 (HMGB1), an abundant nuclear protein in all mammalian cells, affects HIV-1 transcription. Intracellular expression of human HMGB1 repressed HIV-1 gene expression in epithelial cells. This inhibitory effect of HMGB1 was caused by repression of long terminal repeat (LTR)-mediated transcription. Other viral promoters/enhancers, including simian virus 40 or cytomegalovirus, were not inhibited by HMGB1. In addition, HMGB1 inhibition of HIV-1 subtype C expression was dependent on the number of NFκB sites in the LTR region. The inhibitory effect of HMGB1 on viral gene expression observed in HeLa cells was confirmed by an upregulation of viral replication in the presence of antisense HMGB1 in monocytic cells. In contrast to what was found in HeLa cells and monocytic cells, endogenous HMGB1 expression did not affect HIV-1 replication in unstimulated Jurkat cells. Thus, intracellular HMGB1 affects HIV-1 LTR-directed transcription in a promoter- and cell-specific manner.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 179-189 |
| Number of pages | 11 |
| Journal | Virology |
| Volume | 314 |
| Issue number | 1 |
| DOIs | |
| State | Published - Sep 15 2003 |
Funding
We are grateful to Dr. Haichao Wang (Institute for Medical Research, The North Shore Hospital, Manhasset, NY, USA) for his useful discussions on HMGB1. The pCMVHGH plasmid was a generous gift from Dr. G. J. Goodall (Department of Microbiology and Immunology, University of Adelaide, Australia). We also thank Dr. Stephen Goff (Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University, New York) for critical reading of the manuscript. This work was supported by the Swedish Medical Research Council, the Swedish Society for Medicine Research (SSMF), JA:SMRC grant 10850, and by grants from the Karolinska Institutet.
Keywords
- HIV-1 subtypes
- HMGB1
- LTR
- Rel proteins
- Transcription
ASJC Scopus subject areas
- Virology
