Analysis of the role of p7 protein function in hepatitis C virus life cycle

Atoom, Ali (2014) Analysis of the role of p7 protein function in hepatitis C virus life cycle. Doctoral (PhD) thesis, Memorial University of Newfoundland.

[English] PDF (Migrated (PDF/A Conversion) from original format: (application/pdf)) - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. Download (5MB) [English] PDF - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. (Original Version)

Abstract

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.

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