Down regulation of TRIF, TLR3, and MAVS in HCV infected liver correlates with the outcome of infection

作者:Kar Premashis*; Kumar Deepak; Gumma Phani Kumar; Chowdhury Soumya Jyoti; Karra Vijay Kumar
来源:Journal of Medical Virology, 2017, 89(12): 2165-2172.
DOI:10.1002/jmv.24849

摘要

In virus-infected cells, pattern recognition receptors (PRRs) recruits their specific adaptor molecules, mitochondrial antiviral signaling protein (MAVS), TIR-domain-containing adapter-inducing interferon-beta (TRIF), and TNF receptor associated factor (TRAF6) which induces interferon. Toll-like receptor 3 (TLR3) induces activation of the NF-kappa B (NF-kappa B) for interferon production. The study has been designed to assess the correlation of TLR3, MAVS, TRIF, and TRAF6 outcome of HCV infection. The 46 chronic hepatitis C (CHC) patients were screened for LFT (Liver function test), HBsAg, Anti HCV, viral load, histology, and expression of TLR3, MAVS, TRIF, and TRAF6 genes. Out of 46 CHC patients, 7 were on therapy. The 12 healthy controls were screened for LFT, HBsAg, Anti HCV and gene expressions. The gene expressions were studied in liver tissue and measured using semi-quantitative analysis of Western blots. It has been observed that the expression of TRAF6 was independent of HCV infection. The expression of TRIF, TLR3, and MAVS were significantly (P < 0.05) down regulated in CHC (N = 46) compared to healthy controls (N = 12), in high viral load (N = 21) compared to low viral load (N = 25), in HAI (Histology activity index) 1-4 (N = 12), 5-8 (N = 16), 9-12 (N = 8), 13-18 (N = 5) compared to HAI 0 (N = 5) cases. The significant reduction in the expression of TRIF, TLR3, and MAVS was observed in non-responder (N = 3) compared to responder (N = 4) after treatment (P < 0.05). The HCV viral load was positively correlated with the disease severity. The down regulation of TRIF, TLR3, and MAVS expressions in CHC correlates with the disease severity and the outcome of HCV infection.