TAILIEUCHUNG - Báo cáo y học: " Mutations in the E2-PePHD region of hepatitis C virus genotype-3a and correlation with response to interferon and ribavirin combination therapy in Pakistani patients"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Mutations in the E2-PePHD region of hepatitis C virus genotype-3a and correlation with response to interferon and ribavirin combination therapy in Pakistani patients | Afzal et al. Virology Journal 2010 7 377 http content 7 1 377 J VIROLOGY JOURNAL SHORT REPORT Open Access Mutations in the E2-PePHD region of hepatitis C virus genotype-3a and correlation with response to interferon and ribavirin combination therapy in Pakistani patients Samia Afzal Muhammad Idrees Madiha Akram Zunaira Awan Bushra Khubaib Mahwish Aftab Zareen Fatima Sadaf Badar Abrar Hussain Abstract Hepatitis C is a major health problem affecting more than 200 million individuals in the world. Current treatment regimen consisting of interferon alpha and ribavirin does not always succeed in eliminating the virus completely from patient s body. One of the mechanisms by which virus evades the antiviral effect of interferon alpha involves protein kinase PKR eukaryotic initiation factor 2 alpha eIF2a phosphorylation homology domain PePHD . This domain in genotype 1 strains is reportedly homologous to PKR and its target eIF2a. By binding to PKR PePHD inhibits its activity and therefore cause virus to evade antiviral activity of interferon IFN . Many studies have correlated substitutions in this domain to the treatment response and lead to inconclusive results. Some studies suggested that substitutions favor response while others emphasized that no correlation exists. In the present study we therefore compared sequences of PePHD domain of thirty one variants of six hepatitis C virus patients of genotype 3. Three of our HCV 3a infected patients showed rapid virological response to interferon alpha and ribavirin combination therapy whereas the remaining three had breakthrough to the same combination therapy. It is found that PePHD domain is not entirely conserved and has substitutions in some isolates irrespective of the treatment response. However substitution of glutamine Q with Leucine L in one of the breakthrough responders made it more identical to HCV genotype 1a. These substitutions in the breakthrough responders also tended to increase average .

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