Abstract:
:Cellular immune responses (T cell responses) during hepatitis C virus (HCV) infection are significant factors for determining the outcome of infection. HCV adapts to host immune responses by inducing mutations in its genome at specific sites that are important for HLA processing/presentation. Moreover, HCV also adapts to resist potential drugs that are used to restrict its replication, such as direct-acting antivirals (DAAs). Although DAAs have significantly reduced disease burden, resistance to these drugs is still a challenge for the treatment of HCV infection. Recently, drug resistance mutations (DRMs) observed in HCV proteins (NS3/4A, NS5A and NS5B) have heightened concern that the emergence of drug resistance may compromise the effectiveness of DAAs. Therefore, the NS3/4A, NS5A and NS5B drug resistance variations were investigated in this study, and their prevalence was examined in a large number of protein sequences from all HCV genotypes. Furthermore, potential CD4+ and CD8+ T cell epitopes were predicted and their overlap with genetic variations was explored. The findings revealed that many reported DRMs within NS3/4A, NS5A and NS5B are not drug-induced; rather, they are already present in HCV strains, as they were also detected in HCV-naïve patients. This study highlights several hot spots in which HLA and drug selective pressure overlap. Interestingly, these overlapping mutations were frequently observed among many HCV genotypes. This study implicates that knowledge of the host HLA type and HCV subtype/genotype can provide important information in defining personalized therapy.
journal_name
Antiviral Resjournal_title
Antiviral researchauthors
Ikram A,Obaid A,Awan FM,Hanif R,Naz A,Paracha RZ,Ali A,Janjua HAdoi
10.1016/j.antiviral.2016.10.013subject
Has Abstractpub_date
2017-01-01 00:00:00pages
112-124eissn
0166-3542issn
1872-9096pii
S0166-3542(16)30146-2journal_volume
137pub_type
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pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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更新日期:2015-11-01 00:00:00