ArticleMolecular therapy : the journal of the American Society of Gene Therapy2026
Sirtuin2 blockade inhibits replication of human immunodeficiency virus-1 and Mycobacterium tuberculosis in macrophages and humanized mice.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Applications of humanized mice inMolecular medicine reports · 2026Review
- HIV impairs and exploits pulmonary Th17 and Th22 cell-mediated immune responses to Mycobacterium tuberculosis.PLoS pathogens · 2026Article
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14 authors.
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Abstract
Co-infections with Mycobacterium tuberculosis (Mtb) and human immunodeficiency virus-1 (HIV-1) present a critical health challenge and require treatment for patient survival. We found that human M1 macrophages inhibit Mtb growth, while M2 macrophages, characterized by elevated Sirt2 expression, permit Mtb growth. Further, we found that HIV-1 augmented Sirt2 gene expression in MФs. Therefore, we explored the therapeutic potential of sirtuin-modulating drugs using human MФs. Sirtinol, a Sirt2 inhibitor, significantly reduced HIV-1 growth in M0, M1, and M2-MФs by >1log10 over 7 days. Conversely, individual doses of resveratrol and SRT1460, which activate Sirt1, did not affect HIV-1. However, their combination showed a strong synergistic inhibition of HIV-1. The combination of sirtinol with resveratrol was neither synergistic nor antagonistic. Sirtinol upregulated iNOS and ATG5 mRNA in HIV-1-infected MФs in a phenotype-dependent manner. In a humanized mouse model (Hu-NSG-SGM3) co-infected with Mtb H37Rv and the HIV-1 BAL strain, treatment with sirtinol alone, or in combination with combination antiretroviral therapy (cART), showed promising results; sirtinol alone reduced Mtb growth, while its combination with cART effectively inhibited HIV-1 replication in the organs. We propose that Sirt2 blockade and Sirt1-activation represent a novel dual therapeutic strategy for treating HIV-1 and Mtb co-infections.
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