title: Chronic binge alcohol administration dysregulates global regulatory gene networks associated with skeletal muscle wasting in simian immunodeficiency virus-infected macaques.
abstract: BACKGROUND
  There are more than 1 million persons living with HIV/AIDS (PLWHA) in the United States and approximately 40 % of them have a history of alcohol use disorders (AUD). Chronic heavy alcohol consumption and HIV/AIDS both result in reduced lean body mass and muscle dysfunction, increasing the incidence of comorbid conditions. Previous studies from our laboratory using rhesus macaques infected with Simian Immunodeficiency Virus (SIV) demonstrated that chronic binge alcohol (CBA) administration in the absence of antiretroviral therapy exacerbates skeletal muscle (SKM) wasting at end-stage SIV disease. The aim of this study was to characterize how CBA alters global gene regulatory networks that lead to SKM wasting at end-stage disease. Administration of intragastric alcohol or sucrose to male rhesus macaques began 3 months prior to SIV infection and continued throughout the duration of study. High-output array analysis was used to determine CBA-dependent changes in mRNA expression, miRNA expression, and promoter methylation status of SKM at end-stage disease (~10 months post-SIV) from healthy control (control), sucrose-administered, SIV-infected (SUC/SIV), and CBA-administered/SIV-infected (CBA/SIV) macaques.
  
  
  RESULTS
  In addition to previously reported effects on the extracellular matrix and the promotion of a pro-inflammatory environment, we found that CBA adversely affects gene regulatory networks that involve "universal" cellular functions, protein homeostasis, calcium and ion homeostasis, neuronal growth and signaling, and satellite cell growth and survival.
  
  
  CONCLUSIONS
  The results from this study provide an overview of the impact of CBA on gene regulatory networks involved in biological functions, including transcriptional and epigenetic processes, illustrating the genetic and molecular mechanisms associated with CBA-dependent SKM wasting at end-stage SIV infection.
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA. lsimo2@lsuhsc.edu.|LSUHSC-NO Comprehensive Alcohol-HIV/AIDS Research Center (CARC), 1901 Perdido Street, New Orleans, LA, 70112, USA. lsimo2@lsuhsc.edu.
authors.forename: Liz
authors.initials: L
authors.lastname: Simon
authors.affiliation: Department of Genetics, 533 Bolivar Street, New Orleans, LA, 70112, USA. AHolle@lsuhsc.edu.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Hollenbach
authors.affiliation: Department of Pediatrics, Stanley S. Scott Cancer Center, 1700 Tulane Ave., Suite 909, New Orleans, USA. JZabal@lsuhsc.edu.
authors.forename: Jovanny
authors.initials: J
authors.lastname: Zabaleta
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA. pmolin@lsuhsc.edu.|LSUHSC-NO Comprehensive Alcohol-HIV/AIDS Research Center (CARC), 1901 Perdido Street, New Orleans, LA, 70112, USA. pmolin@lsuhsc.edu.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Molina
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage* / Q000494:pharmacology; D020869:Gene Expression Profiling / Q000662:veterinary; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects*; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects*; D009133:Muscular Atrophy / Q000209:etiology / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000662:veterinary; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000473:pathology; D015302:Simian Immunodeficiency Virus; D013395:Sucrose / Q000008:administration & dosage
chemical_list: D000431:Ethanol; D013395:Sucrose