Reply to Pauls et al.: p21 is a master regulator of HIV replication in macrophages through dNTP synthesis block.

Abstract

We thank Pauls et al. for their comments (1) on our article describing that p21 restricts reverse transcription of HIV-1 in monocyte-derived macrophages (MDM) by blocking the synthesis of deoxynucleotides (dNTPs) through the repression of the transcription factor E2F1 and the subsequent inhibition of the expression of ribonucleotide reductase subunit R2 (RNR2) (2). Pauls et al. (1) confirm our finding that p21 blocks HIV replication in MDM, further show that p21 regulates the phosphorylation of SAM domain and HD domain-containing protein 1 (SAMHD1) in MDM, and suggest that p21-mediated restriction in these cells is dependent on SAMHD1. Indeed it has been recently reported that SAMHD1 viral restriction activity, but not its dNTPase activity, is inhibited by CDK1-mediated phosphorylation at residue T592 (3⇓–5). Like Pauls et al. (1), we have found that p21 does regulate SAMHD1 phosphorylation in MDM (Fig. 1). However, we believe that p21 restriction is, at least in MDM, mainly mediated by the block of dNTP synthesis because of RNR2 suppression, which is upstream … [↵][1]2To whom correspondence should be addressed. E-mail: gianfranco.pancino{at}pasteur.fr. [1]: #xref-corresp-1-1