To compare the effects of different genotypes of HIV gp120 and HCV core protein on LX2 hepatic stellate cell line

• Main Authors: Wei-Ting Tang, 湯崴婷
• Other Authors: Jason C. Huang
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/7xsu34

碩士 === 國立陽明大學 === 醫學生物技術暨檢驗學系 === 105 === HCV (Hepatitis C virus) infection is a common cause of liver fibrosis and cirrhosis. Previous studies showed that patients who were infected HCV took averagely 23 years for cirrhosis development and in the HIV/HCV coinfection patients, the progression would shorten to around 7 years. In 2004-2007, Taiwan, there was remarkable increase of injection drug users (IDUs) patients, most of them were HIV/HCV co-infected due to needle sharing. The common subtype of HIV in Taiwan IDU patients is CRF07_BC. Other studies indicated that there was a 7 amino acid deletion in structure protein sequence p6pol and p6gag, which decreased incorporation of Vpr in the virus particle and reduced replication efficiency. In this study, we aimed to know whether HIV CRF07_BC strain would slower liver fibrosis progression compared to other HIV strain such as subtype B. In vitro, we used a HSC (hepatic stellate cell) cell line LX2 to mimic HIV/HCV co-infection by treating recombinant HIV gp120 and HCV core proteins and compared the fibrosis related gene expression between CRF07_BC and other subtypes. In vivo, we collected the clinical data from co-infected patients to compare CD4 count, viral load, FIB_4 and APRI fibrosis score between HIV CRF07_BC and HIV subtype B infected patients. So far we found TGF-β can induce LX2 fibrosis related genes expression, but HIV gp120 did not by real-time PCR. In Western blot, TGF-β can induce α-SMA and collagen protein expression but gp120 proteins from genotype CRF07_BC, IIIB, and isoBaL can only upregulate α-SMA sightly. HCV core protein can induce inflammation gene expression but co-treatment with gp120 did not have additive effects. In vivo, IDU patients who were HIV/HCV co-infection seem to have less CD4 T cells and more FIB_4 score than MSM co-infection patients.　Our preliminary data indicated that LX2 cells activated by gp120 proteins from CRF07_BC or other subtypes expressed similar levels of fibrosis related proteins. We need to recruit more HIV/HCV coinfection patients to determine whether CRF07_BC induced slower fibrosis progression compared with other HIV subtypes.