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Chronic Binge Alcohol and Ovarian Hormone Loss Dysregulate Circulating Immune Cell SIV Co-Receptor Expression and
Patrick M McTernan1,2, Robert W Siggins1,2, Anna Catinis2
1Comprehensive Alcohol Research Center, New Orleans, LA 70112, USA.
Insights
Chronic binge alcohol and ovariectomy increase SIV co-receptor expression on CD4+ T cells in macaques. These factors also disrupt mitochondrial homeostasis, potentially affecting viral reservoirs in SIV-infected females.
Area of Science:
- Immunology
- Virology
- Endocrinology
Background:
- Antiretroviral therapy (ART) has made HIV a chronic condition, with over half of people living with HIV (PLWH) aged 50+. HIV infects CD4+ T cells expressing CCR5 or CXCR4 co-receptors.
- Chronic binge alcohol (CBA) exposure in male macaques increased gut CD4+ T cells expressing the SIV co-receptor CXCR4.
- Gonadal hormone loss is linked to increased activated peripheral T cells, and alcohol disrupts mitochondrial homeostasis, crucial for HIV replication.
Purpose of the Study:
- To investigate if chronic binge alcohol (CBA) and ovariectomy (OVX) increase circulating activated CD4+ T cells expressing SIV co-receptors.
- To determine if CBA and OVX dysregulate mitochondrial homeostasis in SIV-infected female rhesus macaques.
Main Methods:
- Female rhesus macaques were administered chronic binge alcohol (CBA) and/or subjected to ovariectomy (OVX) or sham surgery.
- Flow cytometry and gene expression analysis were used to assess CD4+ T cell counts, SIV co-receptor expression, and mitochondrial homeostasis markers.
Main Results:
- At the study endpoint, CBA-administered macaques (CBA/SHAM) showed increased peripheral CD4+ T cell SIV co-receptor expression and lower CD4+ T cell counts compared to CBA/OVX animals.
- Both CBA and OVX led to altered peripheral immune cell gene expression related to mitochondrial homeostasis.
Conclusions:
- CBA and OVX impact SIV co-receptor expression and CD4+ T cell counts in SIV-infected female macaques.
- These conditions disrupt mitochondrial homeostasis, offering insights into how alcohol use may affect viral expression in cellular reservoirs, especially in ovariectomized macaques.
Abstract:
Effective antiretroviral therapy (ART) has transitioned HIV to a chronic disease, with more than 50% of people living with HIV (PLWH) being over the age of 50. HIV targets activated CD4+ T cells expressing HIV-specific co-receptors (CCR5 and CXCR4). Previously, we reported that chronic binge alcohol (CBA)-administered male rhesus macaques had a higher percentage of gut CD4+ T cells expressing simian immunodeficiency virus (SIV) co-receptor CXCR4. Evidence also suggests that gonadal hormone loss increased activated peripheral T cells. Further, mitochondrial function is critical for HIV replication and alcohol dysregulates mitochondrial homeostasis. Hence, we tested the hypothesis that CBA and ovariectomy (OVX) increase circulating activated CD4+ T cells expressing SIV co-receptors and dysregulate mitochondrial homeostasis in SIV-infected female rhesus macaques. Results showed that at the study end-point, CBA/SHAM animals had increased peripheral CD4+ T cell SIV co-receptor expression, and a lower CD4+ T cell count compared to CBA/OVX animals. CBA and OVX animals had altered peripheral immune cell gene expression important for maintaining mitochondrial homeostasis. These results provide insights into how at-risk alcohol use could potentially impact viral expression in cellular reservoirs, particularly in SIV-infected ovariectomized rhesus macaques.
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