Thymidylate synthase is essential for efficient HIV-1 replication in macrophages

Virology. 2021 Jun 14;561:47-57. doi: 10.1016/j.virol.2021.05.002. Online ahead of print.ABSTRACTThymidylate synthase (TS) is a key enzyme in nucleotide biosynthesis. A study performed by our group on human monocyte-derived macrophages (MDMs) infected with HIV-1 showed that many enzymes related to the folate cycle pathway, such as TS, are upregulated in productively infected cells. Here, we suggest that TS is essential for an effective HIV-1 infection in MDMs. Indeed, a TS specific small interfering RNA (siRNA) as well as the TS specific inhibitor Raltitrexed (RTX) caused a reduction in productively infected cells. Quantitative PCR analysis showed that this treatment decreased the efficacy of the early steps of the viral cycle. The RTX inhibitory effect was counteracted by dNTP addition. These results suggest that TS is essential for the early stages of HIV-1 infection by providing optimal dNTP concentrations in MDMs. TS and its related pathway may thus be considered as a potential therapeutic target for HIV-1 treatment.PMID:34146963 | DOI:10.1016/j.virol.2021.05.002

Source: Virology - June 19, 2021 Category: Virology Authors: Vincent Desrosiers Corinne Barat Yann Breton Michel Ouellet Michel J Tremblay Source Type: research