Alcohol intake alters immune responses and promotes CNS viral persistence in mice

Jennifer Loftis, Jonathan Taylor, Hans Peter Raué, Mark Slifka, Elaine Huang

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Chronic hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic effects, including central nervous system (CNS) damage and neuropsychiatric impairments. Alcohol abuse can exacerbate these adverse effects on brain and behavior, but the molecular mechanisms are not well understood. This study investigated the role of alcohol in regulating viral persistence and CNS immunopathology in mice infected with lymphocytic choriomeningitis virus (LCMV), a model for HCV infections in humans. Female and male BALB/c mice (n = 94) were exposed to alcohol (ethanol; EtOH) and water (or water only) using a two-bottle choice paradigm, followed one week later by infection with either LCMV clone 13 (causes chronic infection similar to chronic HCV), LCMV Armstrong (causes acute infection), or vehicle. Mice were monitored for 60 days post-infection and continued to receive 24-h access to EtOH and water. Animals infected with LCMV clone 13 drank more EtOH, as compared to those with an acute or no viral infection. Six weeks after infection with LCMV clone 13, mice with EtOH exposure evidenced higher serum viral titers, as compared to mice without EtOH exposure. EtOH intake was also associated with reductions in virus-specific CD8+ T cell frequencies (particularly CD11ahi subsets) and evidence of persistent CNS viremia in chronically infected mice. These findings support the hypothesis that EtOH use and chronic viral infection can result in combined toxic effects accelerating CNS damage and neuropsychiatric dysfunction and suggest that examining the role of EtOH in regulating viral persistence and CNS immunopathology in mice infected with LCMV can lead to a more comprehensive understanding of comorbid alcohol use disorder and chronic viral infection.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalBehavioural Brain Research
Volume312
DOIs
StatePublished - Oct 1 2016

Fingerprint

Lymphocytic choriomeningitis virus
Central Nervous System
Virus Diseases
Alcohols
Hepacivirus
Infection
Clone Cells
Chronic Hepatitis C
Water
Poisons
Viremia
Alcoholism
Liver Diseases
Ethanol
Viruses
T-Lymphocytes
Brain
Serum

Keywords

  • Blood brain barrier
  • Ethanol
  • Hepatitis C virus
  • Lymphocytic choriomeningitis virus
  • Neurotoxicity
  • T-cells

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Alcohol intake alters immune responses and promotes CNS viral persistence in mice. / Loftis, Jennifer; Taylor, Jonathan; Raué, Hans Peter; Slifka, Mark; Huang, Elaine.

In: Behavioural Brain Research, Vol. 312, 01.10.2016, p. 1-8.

Research output: Contribution to journalArticle

Loftis, Jennifer ; Taylor, Jonathan ; Raué, Hans Peter ; Slifka, Mark ; Huang, Elaine. / Alcohol intake alters immune responses and promotes CNS viral persistence in mice. In: Behavioural Brain Research. 2016 ; Vol. 312. pp. 1-8.
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