Journal article
SAMHD1 enhances HIV-1-induced apoptosis in monocytic cells via the mitochondrial pathway
mBio, Vol.16(7), e00425-25
07/09/2025
DOI: 10.1128/mbio.00425-25
PMCID: PMC12239581
PMID: 40434097
Abstract
Sterile alpha motif (SAM) and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1) inhibits HIV-1 replication in non-dividing cells by reducing the intracellular dNTP pool. While SAMHD1 is known to promote spontaneous apoptosis, its role in HIV-1-induced apoptosis and the underlying mechanisms remain unclear. In this study, we identify a novel mechanism by which SAMHD1 enhances HIV-1-induced apoptosis in monocytic cells via the mitochondrial pathway. We demonstrate that SAMHD1 enhances apoptosis induced by HIV-1 infection in dividing monocytic THP-1 and U937 cell lines, but not in differentiated macrophage-like cells. Mechanistically, SAMHD1 expression reduces mitochondrial membrane potential and promotes cytochrome c release in HIV-1-infected THP-1 cells, thereby augmenting the mitochondrial apoptotic pathway. Furthermore, SAMHD1-enhanced apoptosis is linked to elevated levels of the pro-apoptotic protein BCL-2-interacting killer (BIK) in cells, which contributes to enhanced apoptosis during HIV-1 infection. These findings reveal a previously unrecognized regulatory role of SAMHD1 in amplifying HIV-1-induced apoptosis in monocytic cells, highlighting its involvement in the mitochondrial apoptotic pathway.IMPORTANCESterile alpha motif (SAM) and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1), a dNTP triphosphohydrolase, lowers intracellular dNTP levels and restricts HIV-1 replication in non-dividing cells. HIV-1 infection induces cell death mainly through apoptosis. While we have shown that endogenous SAMHD1 enhances spontaneous apoptosis in monocytic cells, its role in HIV-1-induced apoptosis and the underlying mechanisms remain unknown. In this study, we aim to bridge this knowledge gap by investigating the functional significance of SAMHD1 in regulating apoptosis during HIV-1 infection of immune cells. Our findings reveal a novel mechanism whereby SAMHD1 enhances HIV-1-induced apoptosis in monocytic cells through the mitochondrial pathway. This suggests a previously unrecognized role of SAMHD1 in modulating cellular responses to HIV-1 infection.
Details
- Title: Subtitle
- SAMHD1 enhances HIV-1-induced apoptosis in monocytic cells via the mitochondrial pathway
- Creators
- Hua Yang - University of IowaPak-Hin Hinson Cheung - University of Iowa, Microbiology and ImmunologyLi Wu - University of Iowa
- Contributors
- Satya Dandekar (Editor)
- Resource Type
- Journal article
- Publication Details
- mBio, Vol.16(7), e00425-25
- DOI
- 10.1128/mbio.00425-25
- PMID
- 40434097
- PMCID
- PMC12239581
- NLM abbreviation
- mBio
- ISSN
- 2150-7511
- eISSN
- 2150-7511
- Publisher
- American Society for Microbiology
- Number of pages
- 22
- Grant note
- R01AI141495, R61AI169659, R21AI170070, R21AI181742, P30CA086862-24S1 / National Institutes of Health (http://dx.doi.org/10.13039/100000002)
- Language
- English
- Electronic publication date
- 05/28/2025
- Date published
- 07/09/2025
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984824164302771
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