Alcohol intake alters immune responses and promotes CNS viral persistence in mice.
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 60days 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 CD11a(hi) 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.
Research & Development Service, Veterans Affairs Portland Health Care System, 3710 SW U.S. Veterans Hospital Rd., Portland, OR 97239, USA; Department of Psychiatry, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA. Electronic address: jennifer.loftis2@va.gov.
Jennifer M
JM
Loftis
Research & Development Service, Veterans Affairs Portland Health Care System, 3710 SW U.S. Veterans Hospital Rd., Portland, OR 97239, USA; Department of Psychiatry, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA. Electronic address: taylorjo@ohsu.edu.
Jonathan
J
Taylor
Division of Neuroscience, Department of Molecular Microbiology and Immunology, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA. Electronic address: raueh@ohsu.edu.
Hans-Peter
HP
Raué
Division of Neuroscience, Department of Molecular Microbiology and Immunology, Oregon National Primate Research Center, Oregon Health & Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA. Electronic address: slifkam@ohsu.edu.
Mark K
MK
Slifka
Research & Development Service, Veterans Affairs Portland Health Care System, 3710 SW U.S. Veterans Hospital Rd., Portland, OR 97239, USA; Department of Psychiatry, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97239, USA. Electronic address: huange@ohsu.edu.
Elaine
E
Huang
D000428:Alcohol Drinking; D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology* / Q000821:virology; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000276:immunology* / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D000431:Ethanol; D001219:Aspartate Aminotransferases
Blood brain barrier; Ethanol; Hepatitis C virus; Lymphocytic choriomeningitis virus; Neurotoxicity; T-cells