title: HIV-1 coinfection profoundly alters intrahepatic chemokine but not inflammatory cytokine profiles in HCV-infected subjects.
abstract: The pathogenesis of accelerated liver damage in subjects coinfected with hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) remains largely unknown. Recent studies suggest that ongoing chronic liver inflammation is responsible for the liver injury in HCV-infected patients. We aimed to determine whether HIV-1 coinfection altered intrahepatic inflammatory profiles in HCV infection, thereby hastening liver damage. We used a real-time RT-PCR-based array to comparatively analyze intrahepatic inflammation gene profiles in liver biopsy specimens from HCV-infected (n = 16), HCV/HIV-1-coinfected (n = 8) and uninfected (n = 8) individuals. We then used human hepatocytes to study the molecular mechanisms underlying alternations of the inflammatory profiles. Compared with uninfected individuals, HCV infection and HCV/HIV-1 coinfection markedly altered expression of 59.5% and 50.0% of 84 inflammation-related genes tested, respectively. Among these genes affected, HCV infection up-regulated the expression of 24 genes and down-regulated the expression of 26 genes, whereas HCV/HIV-1 coinfection up-regulated the expression of 21 genes and down-regulated the expression of 21 genes. Compared with HCV infection, HCV/HIV-1 coinfection did not dramatically affect intrahepatic gene expression profiles of cytokines and their receptors, but profoundly altered expression of several chemokine genes including up-regulation of the CXCR3-associated chemokines. Human hepatocytes produced these chemokines in response to virus-related microbial translocation, viral protein stimulation, and antiviral immune responses.
  
  
  CONCLUSIONS
  HIV-1 coinfection profoundly alters intrahepatic chemokine but not cytokine profiles in HCV-infected subjects. The altered chemokines may orchestrate the tissue-specific and cell-selective trafficking of immune cells and autoimmunity to accelerate liver disease in HCV/HIV-1 coinfection.
authors: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America ; College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.
authors: Sishun
authors: S
authors: Hu
authors: Division of Gastroenterology/Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors: Marwan
authors: M
authors: Ghabril
authors: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors: Tohti
authors: T
authors: Amet
authors: Zhejiang Provincial Key Laboratory for Technology & Application of Model Organisms, Wenzhou Medical College, Wenzhou, Zhejiang, China.
authors: Ningjie
authors: N
authors: Hu
authors: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors: Daniel
authors: D
authors: Byrd
authors: Zhejiang Provincial Key Laboratory for Technology & Application of Model Organisms, Wenzhou Medical College, Wenzhou, Zhejiang, China.
authors: Kai
authors: K
authors: Yang
authors: Division of Gastroenterology/Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors: Raj
authors: R
authors: Vuppalanchi
authors: Department of Pathology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors: Romil
authors: R
authors: Saxena
authors: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America ; Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors: Mona
authors: M
authors: Desai
authors: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors: Jie
authors: J
authors: Lan
authors: Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors: Raymond
authors: R
authors: Johnson
authors: Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors: Samir
authors: S
authors: Gupta
authors: Division of Gastroenterology/Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors: Naga
authors: N
authors: Chalasani
authors: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America ; Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, United States of America ; Center for AIDS Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors: Qigui
authors: Q
authors: Yu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D060085:Coinfection / Q000235:genetics / Q000821:virology*; D003710:Demography; D005260:Female; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000150:complications* / Q000235:genetics / Q000821:virology*; D006526:Hepatitis C / Q000150:complications* / Q000235:genetics / Q000821:virology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000378:metabolism; D055815:Young Adult
chemical_list: C515187:CXCR3 protein, human; D018925:Chemokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D054367:Receptors, CXCR3