An animal model that investigates the mechanisms of combined CNS injury and possible therapeutic strategies for co-morbid alcohol dependence and chronic viral infection

Animal models that provide new insights into the neuroimmunological mechanisms affected by co-morbid alcohol dependence and chronic viral infection are needed. Our recent pilot study of adults with HCV ( n  = 10) found that tumor necrosis factor-alpha and monocyte chemoattractant protein-1 levels were higher in adults who reported more hazardous drinking behavior [determined by the Alcohol Use Disorders Identification Test (AUDIT-C)]. Further, AUDIT-C scores correlated with Beck Depression Inventory scores ( r  = 0.71, p  = 0.039). As an initial step to identify mechanisms by which chronic viral infection and alcohol (ethanol; EtOH) induce abnormalities in immune cell function and contribute to neuropsychiatric impairments, BALB/c mice ( n  = 24) were exposed to EtOH and water (or water only) using a two-bottle choice paradigm, followed one week later by infection with either lymphocytic choriomeningitis virus (LCMV clone 13; a model for HCV infection in humans), LCMV Armstrong (causes acute infection), or vehicle. Mice were monitored for 60 days post-infection and continued to receive 24-hour access to EtOH and water. Six weeks after infection with LCMV clone 13, mice with EtOH exposure evidenced higher serum viral load levels [mean plaque forming units (PFU)/ml  ±  SEM = 15,375  ±  6128)], as compared to mice without EtOH exposure (6500  ±  5252 PFU/ml). Experiments are underway to evaluate the consequences of co-morbidity on T-cell responses, CNS immunopathology, and behavioral impairments.