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© Charles Dauguet
Virus VIH-2, second virus du sida isolé en 1985 par l'équipe du Pr. Montagnier de l'Institut Pasteur.
Publication : Proceedings of the National Academy of Sciences of the United States of America

p21-mediated RNR2 repression restricts HIV-1 replication in macrophages by inhibiting dNTP biosynthesis pathway

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Proceedings of the National Academy of Sciences of the United States of America - 30 Sep 2013

Allouch A, David A, Amie SM, Lahouassa H, Chartier L, Margottin-Goguet F, Barré-Sinoussi F, Kim B, Sáez-Cirión A, Pancino G

Link to Pubmed [PMID] – 24082141

Proc. Natl. Acad. Sci. U.S.A. 2013 Oct;110(42):E3997-4006

Macrophages are a major target cell for HIV-1, and their infection contributes to HIV pathogenesis. We have previously shown that the cyclin-dependent kinase inhibitor p21 inhibits the replication of HIV-1 and other primate lentiviruses in human monocyte-derived macrophages by impairing reverse transcription of the viral genome. In the attempt to understand the p21-mediated restriction mechanisms, we found that p21 impairs HIV-1 and simian immunodeficiency virus (SIV)mac reverse transcription in macrophages by reducing the intracellular deoxyribonucleotide (dNTP) pool to levels below those required for viral cDNA synthesis by a SAM domain and HD domain-containing protein 1 (SAMHD1)-independent pathway. We found that p21 blocks dNTP biosynthesis by down-regulating the expression of the RNR2 subunit of ribonucleotide reductase, an enzyme essential for the reduction of ribonucleotides to dNTP. p21 inhibits RNR2 transcription by repressing E2F1 transcription factor, its transcriptional activator. Our findings unravel a cellular pathway that restricts HIV-1 and other primate lentiviruses by affecting dNTP synthesis, thereby pointing to new potential cellular targets for anti-HIV therapeutic strategies.

http://www.ncbi.nlm.nih.gov/pubmed/24082141