Atoom, Ali (2014) Analysis of the role of p7 protein function in hepatitis C virus life cycle. Doctoral (PhD) thesis, Memorial University of Newfoundland.
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The hepatitis C virus genome encodes a 63 amino acid protein, p7. The exact role of p7 is unknown; in this study we observed that mutations in transmembrane domain-1 and -2 (TM1 and TM2), and the cytoplasmic loop of p7 decreased infectious virus production. Analysis of p7 at different stages of virus assembly revealed that p7 functions at a stage prior to generation of infectious particles. Confocal microscopy analyses indicated that p7 did not affect recruitment of core protein to lipid droplets. Additionally, mutation of p7 did not affect formation of core multi-order structures. Finally, mutations at the cytoplasmic loop significantly reduced intracellular E2 glycoprotein levels. Forced evolution analysis of p7 mutations resulted in the occurrence of a N765D mutation that was important for secretion of virus particles into the culture supernatants. The results of this study provide strong evidence that p7 functions to protect HCV glycoproteins from premature degradation and we suggest that p7 supports the virus assembly process.
|Item Type:||Thesis (Doctoral (PhD))|
|Additional Information:||Includes bibliographical references (pages 128-148).|
|Department(s):||Medicine, Faculty of|
|Library of Congress Subject Heading:||Hepatitis C virus--Genetics; Viral proteins--Analysis; Microbial mutation; Hepatitis C virus--Life cycles|
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