HIV-1 Tat-Mediated Human Müller Glial Cell Senescence Involves Endoplasmic Reticulum Stress and Dysregulated Autophagy.
Uma Maheswari DeshettyNivedita ChatterjeeShilpa BuchPalsamy PeriyasamyPublished in: Viruses (2024)
Antiretroviral treatments have notably extended the lives of individuals with HIV and reduced the occurrence of comorbidities, including ocular manifestations. The involvement of endoplasmic reticulum (ER) stress in HIV-1 pathogenesis raises questions about its correlation with cellular senescence or its role in initiating senescent traits. This study investigated how ER stress and dysregulated autophagy impact cellular senescence triggered by HIV-1 Tat in the MIO-M1 cell line (human Müller glial cells). Cells exposed to HIV-1 Tat exhibited increased vimentin expression combined with markers of ER stress (BiP, p-eIF2α), autophagy (LC3, Beclin-1, p62), and the senescence marker p21 compared to control cells. Western blotting and staining techniques like SA-β-gal were employed to examine these markers. Additionally, treatments with ER stress inhibitor 4-PBA before HIV-1 Tat exposure led to a decreased expression of ER stress, senescence, and autophagy markers. Conversely, pre-treatment with the autophagy inhibitor 3-MA resulted in reduced autophagy and senescence markers but did not alter ER stress markers compared to control cells. The findings suggest a link between ER stress, dysregulated autophagy, and the initiation of a senescence phenotype in MIO-M1 cells induced by HIV-1 Tat exposure.
Keyphrases
- endoplasmic reticulum stress
- induced apoptosis
- hiv positive
- antiretroviral therapy
- hiv infected
- endothelial cells
- human immunodeficiency virus
- cell death
- hiv testing
- signaling pathway
- cell cycle arrest
- hiv aids
- hepatitis c virus
- oxidative stress
- men who have sex with men
- dna damage
- poor prognosis
- stress induced
- stem cells
- risk assessment
- hiv infected patients
- cell proliferation
- endoplasmic reticulum
- single cell
- long non coding rna
- bone marrow
- smoking cessation
- atomic force microscopy