title: Metabolic Dysregulation in Hepacivirus Infection of Common Marmosets (Callithrix jacchus).
abstract: Chronic hepatitis C has been associated with metabolic syndrome that includes insulin resistance, hepatic steatosis and obesity. These metabolic aberrations are risk factors for disease severity and treatment outcome in infected patients. Experimental infection of marmosets with GBV-B serves as a tangible, small animal model for human HCV infection, and while virology and pathology are well described, a full investigation of clinical disease and the metabolic milieu is lacking. In this study six marmosets were infected intravenously with GBV-B and changes in hematologic, serum biochemical and plasma metabolic measures were investigated over the duration of infection. Infected animals exhibited signs of lymphocytopenia, but platelet and RBC counts were generally stable or even increased. Although most animals showed a transient decline in blood glucose, infection resulted in several fold increases in plasma insulin, glucagon and glucagon-like peptide 1 (GLP-1). All infected animals experienced transient weight loss within the first 28 days of infection, but also became hypertriglyceridemic and had up to 10-fold increases in adipocytokines such as resistin and plasminogen activator inhibitor 1 (PAI-1). In liver, moderate to severe cytoplasmic changes associated with steatotic changes was observed microscopically at 168 days post infection. Collectively, these results suggest that GBV-B infection is accompanied by hematologic, biochemical and metabolic abnormalities that could lead to obesity, diabetes, thrombosis and atherosclerosis, even after virus has been cleared. Our findings mirror those found in HCV patients, suggesting that metabolic syndrome could be conserved among hepaciviruses, and both mechanistic and interventional studies for treating HCV-induced metabolic complications could be evaluated in this animal model.
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Cordelia
authors.initials: C
authors.lastname: Manickam
authors.affiliation: New England Primate Research Center, Harvard Medical School, Southborough Campus, Southborough, Massachusetts, United States of America.
authors.forename: Lynn
authors.initials: L
authors.lastname: Wachtman
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Martinot
authors.affiliation: Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, Texas, United States of America.
authors.forename: Luis D
authors.initials: LD
authors.lastname: Giavedoni
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.|New England Primate Research Center, Harvard Medical School, Southborough Campus, Southborough, Massachusetts, United States of America.
authors.forename: R Keith
authors.initials: RK
authors.lastname: Reeves
mesh_terms: D000818:Animals; D001786:Blood Glucose; D002144:Callithrix / Q000378:metabolism / Q000821:virology*; D005260:Female; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000378:metabolism; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008659:Metabolic Diseases / Q000150:complications* / Q000821:virology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon