ABSTRACT
Background: Interferon therapy is an expensive treatment for hepatitis C virus [HCV] which may results in undesirable side effects. About 50% of chronic HCV patients do not respond to interferon [IFN] therapy for unknown reasons. It is important to determine the association of clinical parameters with IFNAR-2 in HCV patients, resistant to IFN therapy
Methods: HCV genotype 3 patients were included in study [n=20, between 30-60 age group] and categorized into two groups, the experimental group including patients responding to interferon treatment and the control group consisting of interferon resistant patients. Blood samples and Liver biopsy specimens were collected from all HCV patients. Clinical parameters included in the study were [i] pre-biopsy tests [platelet count, bleeding time, prothrombin time] [ii] HCV viral genotype 3 [iii] HCV-RNA and [iv] liver functions [ALT, ALP, and bilirubin]. Molecular investigations were carried out by using PCR and gel electrophoresis to identify IFNAR-2 in all HCV genotype 3 patients
Results: Experimental results from clinical testing of non-responder [resistant] group, showed significantly increased ALT level [64.13+/-17.48 U/L] as compared to responder group [46+/-6.3 U/L]. Hemoglobin [Hb] level was also found significantly increased in non-responder group [12.9+/-1.8 g/dL] in comparison with responder group [10.3+/-0.48 g/dL]. Further molecular testing revealed that all interferon resistant patients showed the presence of IFNAR-2
Conclusion: Experimental observations revealed that non-responder HCV genotype 3 patients showed elevated ALT and Hb levels and presence of IFNAR-2 protein. Therefore, experimental results of this study signify the importance of monitoring clinical parameters in parallel with IFN therapy in non-responder HCV patients
ABSTRACT
Background: Structural analysis of human interferon alpha receptor 2 [IFNAR-2] protein is important to determine its structure and function because that information is needed to understand the role and mechanism of IFNAR-2 protein in human immune system. Therefore, this study was conducted to find out composition of amino acids contributing in primary and secondary structure of IFNAR-2 protein
Methods: Protein sequences of human IFNAR-2 were retrieved from The Universal Protein Resource [UniProt]'s and National Center for Biotechnology Information [NCBI]'s databases. The Basic Local Alignment Search Tool [BLAST] was used to search for every IFNAR-2 protein sequence in NCBI database. Human IFNAR-2 protein sequences were further refined according to set criteria for experimental analysis. All retrieved IFNAR-2 protein sequences were aligned by using computational tool Clustal Omega Consensus protein sequence was obtained from aligned protein dataset. Furthermore, consensus protein sequence of IFNAR-2 was subjected for secondary structure prediction analysis. Protein topology was predicted by using Expert Protein Analysis System [ExPASy] server and Transmembrane Helices; Hidden Markov Model
Results: Alignment data set revealed that IFNAR-2 protein consisted of 515 amino acids long chain, having total 37 identical positions with 6.446% identity. Protein topology analysis predicted that human IFNAR-2 protein consists of verities of secondary structures such as alpha-helix, turn and beta sheets. Alpha-helixes mainly form three topological domains [i] inner [1-6 amino acids], [ii] outer [7-29 amino acids] and [iii] trans-membrane domain [30-515 amino acids]
Conclusion: Human IFNAR-2 protein consists of 515 amino acids having hydrophobic, polar and aromatic characteristics. Alpha-helixes, turn, beta sheets and three topological domains constitute secondary structure and predicted topological domains contribute in the subcellular compartmentalization