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Updated: Nov 1, 2025

Isolation, Transfection, and Culture of Primary Human Monocytes
Published on: December 16, 2019
Thymidylate synthase is essential for efficient HIV-1 replication in macrophages
Vincent Desrosiers1, Corinne Barat1, Yann Breton1
1Axe des Maladies Infectieuses et Immunitaires, Centre de Recherche Du CHU de Québec-Université Laval, Pavillon CHUL, Québec, QC, G1V 4G2, Canada.
Abstract:
Thymidylate 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.
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