Chronic Binge Alcohol and Ovarian Hormone Loss Dysregulate Circulating Immune Cell SIV Co-Receptor Expression and Mitochondrial Homeostasis in SIV-Infected Rhesus Macaques

Biomolecules. 2022 Jul 5;12(7):946. doi: 10.3390/biom12070946.


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.

Keywords: CCR5; CD4+ T cell; CXCR4; HIV; SIV; alcohol; mitochondria; ovariectomy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Ethanol
  • Female
  • Gene Expression
  • HIV Infections*
  • Homeostasis
  • Hormones
  • Humans
  • Macaca mulatta
  • Male
  • Mitochondria / metabolism
  • Simian Acquired Immunodeficiency Syndrome*
  • Simian Immunodeficiency Virus* / genetics


  • Hormones
  • Ethanol