The expression of cellular proteins modulated by GRIM19 overexpression was tested by Western blot analysis. Results: In the present study, GRIM19 expression was down-regulated not only in FR1 and SR1 cells but also in tissues of http://www.selleckchem.com/products/ABT-263.html the patients with chronic HCV infection. Furthermore, our results showed that GRIM19 overexpression significantly decreased lipid accumulation in oleic acid-treated cells and reduced HCV RNA replication in FR1 and SR1 cells to 40∼60 %. Ectopically expressed GRIM19 in HCV replicating cells
enhanced the activity of AMPactivated protein kinase (AMPK), a key regulator of lipid metab-olism. Conclusion: Our results demonstrated that HCV downregulated the level of GRIM19 to maintain the suitable microenvironment for its replication. Also, overexpression of GRIM19 reduced HCV replication by abrogation of lipid accumulation though regulation of AMPK pathway. In conclusion, these results suggest that GRIM19 might be exploited for the development of novel antiviral agents. Disclosures: The following people have nothing to disclose: Jung-Hee Kim, Wonhee Hur, Jung Eun Choi, Eun Byul Lee, Tian Zhu Li, Sung Woo
Kim, Sung Woo Hong, Young Ki Lee, Sung Min Kim, Joon Ho Lee, Sung Won Lee, Pil Soo Sung, Eui-Cheol Shin, Seung Kew Yoon Purpose: Attributes of the first 500 patient samples tested in a commercially available genotypic NS3/4A protease inhibitor (PI) resistance assay Ivacaftor research buy for HCV genotype 1(GT1) were previously reported. This study compares telaprevir (TVR) and boceprevir (BOC) resistance trends in the first 1500 samples to prior results and examines the prevalence of Q80 substitutions, which are not associated
with resistance to TVR or BOC, but are associated with resistance to simeprevir (SMV), a second generation HCV PI. Methods: HCV GT1a or GT1b patient samples with viral loads > 2000 lU/mL were sent to Monogram Glycogen branching enzyme Biosciences for PI resistance analysis using the HCV GenoSure® NS3/4A resistance assay. Briefly, the entire nonstructural protein 3 (NS3) and 4A (NS4A) region of HCV was amplified by RT-PCR using GT1 a or GT1 b specific primers, analyzed by population sequencing and compared to either the H77 (GT1a) or Con 1 (GT1b) reference sequence. Resistance-associated variants (RAVs) were identified and a prediction of drug susceptibility was derived using a rules-based algorithm. The HCV genotype of the NS3/4A region was also determined. Results: The trends observed in the initial 500 samples remained consistent with the addition of 1000 more samples. of the 1500 samples analyzed, 77% were GT1a and 23% were GT1 b. Overall predicted resistance to both TVR and BoC was 22%; 20% and 21% for TVR and BOC, respectively, in GT1a patient samples, but only 2% and 3%, respectively, in GT1b samples. The most commonly observed RAVs for both drugs were R155K (14.
No related posts.