Chronic binge alcohol administration dysregulates peripheral blood mononuclear cell (PBMC) mitochondrial gene expression in SIV infection
Location
Medical Education Building, LSUHSC-NO
Presentation Date
10-10-2019 10:00 AM
End Date
10-10-2019 12:00 PM
Description
Alcohol use disorder (AUD) is highly prevalent in persons living with Human Immunodeficiency Virus (PLWH). With antiretroviral therapy, PLWH are living longer, increasing risks of geriatric comorbidities. Mitochondrial homeostasis including optimal substrate utilization and energy production is critical in PBMCs, particularly CD8 T cells. Optimal T cell function is critical to destroy HIV infected CD4 T cells.1 We have previously shown that chronic binge alcohol (CBA) dysregulates skeletal muscle (SKM) mitochondrial gene expression and mitochondrial function in simian immune deficiency (SIV)-infected macaques.2 Therefore, the objective of this study sought to investigate whether CBA administration dysregulates PBMC mitochondrial gene expression. Moreover, if PBMC mitochondrial function can be directly correlated to tissue mitochondrial function, these cells could potentially be used as a non¬invasive clinical surrogate marker of tissue mitochondrial dyshomeostasis. Female rhesus macaques were infused daily with intragastric alcohol or water three months prior to SIV infection and continued for the duration of the study. After 2.5 months, macaques received antiretroviral therapy and the study was continued until 8 months post SIV infection. Blood samples were collected at various time points during the study. PBMCs were isolated and RNA was extracted and converted into cDNA for qPCR analysis of mitochondrial genes. CBA significantly decreased expression of PGC1, a master regulator of mitochondrial biogenesis and respiration, and NRF2, a regulator of antioxidant protein expression. Our results support the hypothesis that CBA dysregulates PBMC mitochondrial gene expression in SIV infection. Future studies will determine the role of PBMC mitochondrial gene dysregulation on metabolic dyshomeostasis and whether therapeutic interventions that boost mitochondrial homeostasis improve PBMC, especially T cell, function.
Recommended Citation
Catinis, Anna M., "Chronic binge alcohol administration dysregulates peripheral blood mononuclear cell (PBMC) mitochondrial gene expression in SIV infection" (2019). Medical Student Research Poster Symposium. 6.
https://digitalscholar.lsuhsc.edu/sommrd/2019/posters/6
Chronic binge alcohol administration dysregulates peripheral blood mononuclear cell (PBMC) mitochondrial gene expression in SIV infection
Medical Education Building, LSUHSC-NO
Alcohol use disorder (AUD) is highly prevalent in persons living with Human Immunodeficiency Virus (PLWH). With antiretroviral therapy, PLWH are living longer, increasing risks of geriatric comorbidities. Mitochondrial homeostasis including optimal substrate utilization and energy production is critical in PBMCs, particularly CD8 T cells. Optimal T cell function is critical to destroy HIV infected CD4 T cells.1 We have previously shown that chronic binge alcohol (CBA) dysregulates skeletal muscle (SKM) mitochondrial gene expression and mitochondrial function in simian immune deficiency (SIV)-infected macaques.2 Therefore, the objective of this study sought to investigate whether CBA administration dysregulates PBMC mitochondrial gene expression. Moreover, if PBMC mitochondrial function can be directly correlated to tissue mitochondrial function, these cells could potentially be used as a non¬invasive clinical surrogate marker of tissue mitochondrial dyshomeostasis. Female rhesus macaques were infused daily with intragastric alcohol or water three months prior to SIV infection and continued for the duration of the study. After 2.5 months, macaques received antiretroviral therapy and the study was continued until 8 months post SIV infection. Blood samples were collected at various time points during the study. PBMCs were isolated and RNA was extracted and converted into cDNA for qPCR analysis of mitochondrial genes. CBA significantly decreased expression of PGC1, a master regulator of mitochondrial biogenesis and respiration, and NRF2, a regulator of antioxidant protein expression. Our results support the hypothesis that CBA dysregulates PBMC mitochondrial gene expression in SIV infection. Future studies will determine the role of PBMC mitochondrial gene dysregulation on metabolic dyshomeostasis and whether therapeutic interventions that boost mitochondrial homeostasis improve PBMC, especially T cell, function.
Comments
Mentor: Dr. Patricia Molina (Department of Physiology)