Chronic alcohol accentuates nutritional, metabolic, and immune alterations during asymptomatic simian immunodeficiency virus infection

Patricia E. Molina, Margaret McNurlan, John Rathmacher, Charles H. Lang, Kirsten L. Zambell, Jeanette Purcell, Rudolf P. Bohm, Ping Zhang, Gregory J. Bagby, Steve Nelson

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Background: Alcohol abuse has been reported to have a high prevalence in the human immunodeficiency virus (HIV)-infected population. However, its impact on disease progression is unknown. Studies dissecting the drug-induced or alcohol-induced metabolic derangements that are likely to alter the course of disease progression are lacking. This is particularly important because of the substantial reduction in morbidity and mortality of patients on highly active antiretroviral therapy (HAART). HIV infection has become a more chronic disease during which alcohol-induced metabolic alterations may become more prevalent and pronounced. Methods: The present study used a model of chronic intragastric alcohol administration initiated 3 months before intravenous simian immunodeficiency (SIV) inoculation and continued thereafter throughout the course of SIV infection, to investigate the impact of chronic alcohol binge-like consumption during the initial 10-month asymptomatic phase of SIV infection in nonhuman primate rhesus macaques. Anthropometric, metabolic, biochemical, nutritional, and immune state indicators were examined before infection and at 3-month intervals in asymptomatic chronic alcohol-treated SIV-infected macaques and time-matched isocaloric and uninfected controls. Results: Intravenous SIVΔB670 infection resulted in increased viral load, decreased circulating CD4+/CD8+ lymphocyte ratio, and increased lymphocyte proliferation (Ki67/CD3+). Chronic alcohol/SIV+ animals showed a higher viral load at 3 months post-SIV infection as well as a significant and early decrease in caloric intake and nitrogen balance associated with a change in food choice. Rates of skeletal muscle protein synthesis and breakdown, mRNA expression of IGF-I, myostatin, or the ubiquitin ligase muscle atrophy F-box protein (MAFbx) did not differ from basal during the 10-month asymptomatic period of infection. However, muscle TNF-α mRNA expression was markedly increased at 10 months post-SIV infection in alcohol/SIV+ animals. Discussion: These findings suggest that chronic alcohol accelerates nutritional and metabolic dysregulation during SIV infection and may favor a skeletal muscle proinflammatory state, possibly conducive to subsequent muscle wasting.

Original languageEnglish (US)
Pages (from-to)2065-2078
Number of pages14
JournalAlcoholism: Clinical and Experimental Research
Volume30
Issue number12
DOIs
StatePublished - Dec 1 2006

Fingerprint

Simian Immunodeficiency Virus
Virus Diseases
Viruses
Alcohols
Infection
Muscle
Lymphocytes
Viral Load
Disease Progression
Skeletal Muscle
F-Box Proteins
HIV
Animals
Myostatin
Muscles
CD4-CD8 Ratio
Messenger RNA
Asymptomatic Infections
Muscular Atrophy
Muscle Proteins

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

Molina, Patricia E. ; McNurlan, Margaret ; Rathmacher, John ; Lang, Charles H. ; Zambell, Kirsten L. ; Purcell, Jeanette ; Bohm, Rudolf P. ; Zhang, Ping ; Bagby, Gregory J. ; Nelson, Steve. / Chronic alcohol accentuates nutritional, metabolic, and immune alterations during asymptomatic simian immunodeficiency virus infection. In: Alcoholism: Clinical and Experimental Research. 2006 ; Vol. 30, No. 12. pp. 2065-2078.
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abstract = "Background: Alcohol abuse has been reported to have a high prevalence in the human immunodeficiency virus (HIV)-infected population. However, its impact on disease progression is unknown. Studies dissecting the drug-induced or alcohol-induced metabolic derangements that are likely to alter the course of disease progression are lacking. This is particularly important because of the substantial reduction in morbidity and mortality of patients on highly active antiretroviral therapy (HAART). HIV infection has become a more chronic disease during which alcohol-induced metabolic alterations may become more prevalent and pronounced. Methods: The present study used a model of chronic intragastric alcohol administration initiated 3 months before intravenous simian immunodeficiency (SIV) inoculation and continued thereafter throughout the course of SIV infection, to investigate the impact of chronic alcohol binge-like consumption during the initial 10-month asymptomatic phase of SIV infection in nonhuman primate rhesus macaques. Anthropometric, metabolic, biochemical, nutritional, and immune state indicators were examined before infection and at 3-month intervals in asymptomatic chronic alcohol-treated SIV-infected macaques and time-matched isocaloric and uninfected controls. Results: Intravenous SIVΔB670 infection resulted in increased viral load, decreased circulating CD4+/CD8+ lymphocyte ratio, and increased lymphocyte proliferation (Ki67/CD3+). Chronic alcohol/SIV+ animals showed a higher viral load at 3 months post-SIV infection as well as a significant and early decrease in caloric intake and nitrogen balance associated with a change in food choice. Rates of skeletal muscle protein synthesis and breakdown, mRNA expression of IGF-I, myostatin, or the ubiquitin ligase muscle atrophy F-box protein (MAFbx) did not differ from basal during the 10-month asymptomatic period of infection. However, muscle TNF-α mRNA expression was markedly increased at 10 months post-SIV infection in alcohol/SIV+ animals. Discussion: These findings suggest that chronic alcohol accelerates nutritional and metabolic dysregulation during SIV infection and may favor a skeletal muscle proinflammatory state, possibly conducive to subsequent muscle wasting.",
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Chronic alcohol accentuates nutritional, metabolic, and immune alterations during asymptomatic simian immunodeficiency virus infection. / Molina, Patricia E.; McNurlan, Margaret; Rathmacher, John; Lang, Charles H.; Zambell, Kirsten L.; Purcell, Jeanette; Bohm, Rudolf P.; Zhang, Ping; Bagby, Gregory J.; Nelson, Steve.

In: Alcoholism: Clinical and Experimental Research, Vol. 30, No. 12, 01.12.2006, p. 2065-2078.

Research output: Contribution to journalArticle

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T1 - Chronic alcohol accentuates nutritional, metabolic, and immune alterations during asymptomatic simian immunodeficiency virus infection

AU - Molina, Patricia E.

AU - McNurlan, Margaret

AU - Rathmacher, John

AU - Lang, Charles H.

AU - Zambell, Kirsten L.

AU - Purcell, Jeanette

AU - Bohm, Rudolf P.

AU - Zhang, Ping

AU - Bagby, Gregory J.

AU - Nelson, Steve

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Y1 - 2006/12/1

N2 - Background: Alcohol abuse has been reported to have a high prevalence in the human immunodeficiency virus (HIV)-infected population. However, its impact on disease progression is unknown. Studies dissecting the drug-induced or alcohol-induced metabolic derangements that are likely to alter the course of disease progression are lacking. This is particularly important because of the substantial reduction in morbidity and mortality of patients on highly active antiretroviral therapy (HAART). HIV infection has become a more chronic disease during which alcohol-induced metabolic alterations may become more prevalent and pronounced. Methods: The present study used a model of chronic intragastric alcohol administration initiated 3 months before intravenous simian immunodeficiency (SIV) inoculation and continued thereafter throughout the course of SIV infection, to investigate the impact of chronic alcohol binge-like consumption during the initial 10-month asymptomatic phase of SIV infection in nonhuman primate rhesus macaques. Anthropometric, metabolic, biochemical, nutritional, and immune state indicators were examined before infection and at 3-month intervals in asymptomatic chronic alcohol-treated SIV-infected macaques and time-matched isocaloric and uninfected controls. Results: Intravenous SIVΔB670 infection resulted in increased viral load, decreased circulating CD4+/CD8+ lymphocyte ratio, and increased lymphocyte proliferation (Ki67/CD3+). Chronic alcohol/SIV+ animals showed a higher viral load at 3 months post-SIV infection as well as a significant and early decrease in caloric intake and nitrogen balance associated with a change in food choice. Rates of skeletal muscle protein synthesis and breakdown, mRNA expression of IGF-I, myostatin, or the ubiquitin ligase muscle atrophy F-box protein (MAFbx) did not differ from basal during the 10-month asymptomatic period of infection. However, muscle TNF-α mRNA expression was markedly increased at 10 months post-SIV infection in alcohol/SIV+ animals. Discussion: These findings suggest that chronic alcohol accelerates nutritional and metabolic dysregulation during SIV infection and may favor a skeletal muscle proinflammatory state, possibly conducive to subsequent muscle wasting.

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