Systems Biological Analyses Reveal the Hepatitis C Virus (HCV)-Specific Regulation of Hematopoietic Development

Velazquez VM, Uebelhoer LS, Thapa M, Ibegbu CC, Courtney C, Bosinger SE, Magliocca JF, Adams AB, Kirk AD, Knechtle SJ, Kalman D, Suthar MS, Grakoui A. Hepatology. (2015) 61, 843-856.

Speaker：Yu-ling Chen (陳又菱)                                        Time：15:10~16:00, Dec. 2, 2015

Commentator：Dr. Kung-Chia Young (楊孔嘉教授)     &nnbsp;    Place：Room 601

Abstract

Hepatitis C virus (HCV) infection can cause a short-term illness but for 70%–85% of people may become a long-term chronic HCV infection. Chronic hepatitis C can result in long-term inflammation that majorly targets liver and even leads to hepatocellular carcinoma. Liver plays an important role in detoxification, and is also associated with cell composition and blood supply. The immune tolerance of liver relates to the pathogenesis of many liver diseases, such as HCV-infection and the development of systemic diseases. According to previous findings, the author demonstrated that human liver leukocytes expressed hematopoietic cell maker, CD34.¹ Human liver contains CD34+lineage- cells which are source of hematopoietic cells. The CD34+lineage- cells showed hematopoietic characteristics such as abilities of proliferation and differentiation.¹ In this study, the author further evaluate the hematopoietic capabilities of CD34+ cells in subject with nonalcoholic steatohepatitis (NASH), chronic HCV and alcohol liver disease (ALD). Two primary subsets, CD34+ CD146+ and CD34+CD146- cells, were found. CD34+CD146- cells exhibited hematopoietic function but not CD34+CD146+ cells. However, CD34+CD146+ cells showed higher endothelial gene expression and no significant differences on gene expression of ALD and HCV subjects. On gene signatures of chronic HCV, CD34+CD146- cells were highly associated with genes of cell cycle, DNA damage, DNA repair, development, chemotaxis and immune response, especially in B cell and myeloid cell lineages. Thus, HCV infection may have superior effects on hematopoiesis as compared with NASH and ALD. Intrahepatic CD34+CD146- cells were programmed to neutrophilic and monocytic progeny. Disease-specific alterations of hematopoiesis were observed among chronic HCV, NASH and ALD. Moreover, HCV viral load had negative correlation between liver CD34+ frequency.In conclusion, liver hematopoietic cells could be therapeutic targets for liver-associated diseases.

References：

1.     Velazquez VM, Hon H, Ibegbu C, Knechtle SJ, Kirk AD, Grakoui A. (2012) Hepatic enrichment and activation of myeloid dendritic cells during chronic hepatitis C virus infection. Hepatology. 56, 2071-2081.