p21-mediated RNR2 repression restricts HIV-1 replication in macrophages by inhibiting dNTP biosynthesis pathway
Abstract
Macrophages, with CD4+ T lymphocytes, are a major cell target for HIV-1 infection. We have previously reported that the induction of a cellular protein, the cyclin-dependent kinase p21, inhibits HIV-1 replication in macrophages. We now show that p21 impairs the reverse transcription of HIV-1 and other primate lentiviruses, including the simian immunodeficiency virus (SIV)mac, by blocking the synthesis of cellular deoxynucleotides (dNTP) that are used by retroviral reverse transcriptase for viral DNA synthesis. p21 represses the expression of a key enzyme of the dNTP biosynthesis pathway, the RNR2 subunit of the ribonucleotide reductase. Our findings point to new potential cellular targets for antiretroviral strategies.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- October 2013
- DOI:
- 10.1073/pnas.1306719110
- Bibcode:
- 2013PNAS..110E3997A