SAMHD1 enhances HIV-1-induced apoptosis in monocytic cells via the mitochondrial pathway

Hua Yang; Pak-Hin Hinson Cheung; Li Wu

doi:10.1101/2025.01.08.632057

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SAMHD1 enhances HIV-1-induced apoptosis in monocytic cells via the mitochondrial pathway

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SAMHD1 enhances HIV-1-induced apoptosis in monocytic cells via the mitochondrial pathway

Hua Yang, Pak-Hin Hinson Cheung and Li Wu

bioRxiv

Cold Spring Harbor Laboratory

01/09/2025

DOI: 10.1101/2025.01.08.632057

PMCID: PMC11741301

PMID: 39829911

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https://doi.org/10.1101/2025.01.08.632057View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

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. SAMHD1 enhances spontaneous apoptosis in cells, but its effects on HIV-1-induced apoptosis and the underlying mechanisms remain unknown. Here we uncover a new mechanism by which SAMHD1 enhances HIV-1-induced apoptosis in monocytic cells through the mitochondrial pathway. We found that endogenous SAMHD1 enhances apoptosis levels induced by HIV-1 infection in dividing THP-1 cells. Mechanistically, SAMHD1 expression decreases the mitochondrial membrane potential and promotes cytochrome c release induced by HIV-1 infection in THP-1 cells, thereby enhancing mitochondrial apoptotic pathway. SAMHD1-enhanced apoptosis is associated with increased expression of the pro-apoptotic protein BCL-2-interacting killer (BIK) in cells. We further demonstrated that BIK contributes to SAMHD1-enhanced apoptosis during HIV-1 infection. Overall, our results reveal an unappreciated regulatory mechanism of SAMHD1 in enhancing HIV-1-induced apoptosis via the mitochondrial pathway in monocytic cells.

Apoptosis

monocytic cells

HIV-1 infection

BCL-2-interacting killer

mitochondrial membrane potential

THP-1 cells

mitochondrial pathway

SAMHD1

cytochrome c

Details

Title: Subtitle: SAMHD1 enhances HIV-1-induced apoptosis in monocytic cells via the mitochondrial pathway
Creators: Hua Yang - University of Iowa
Pak-Hin Hinson Cheung - University of Iowa, Microbiology and Immunology
Li Wu - University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv
DOI: 10.1101/2025.01.08.632057
PMID: 39829911
PMCID: PMC11741301
NLM abbreviation: bioRxiv
ISSN: 2692-8205
eISSN: 2692-8205
Publisher: Cold Spring Harbor Laboratory; United States
Grant note: R21 AI181742 / NIAID NIH HHS R61 AI169659 / NIAID NIH HHS R01 AI141495 / NIAID NIH HHS P30 CA086862 / NCI NIH HHS R21 AI170070 / NIAID NIH HHS
Language: English
Date posted: 01/09/2025
Academic Unit: Microbiology and Immunology
Record Identifier: 9984775264902771

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