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Identification and comparative analysis of hepatitis C virus-host cell protein interactions.

Publication ,  Journal Article
Dolan, PT; Zhang, C; Khadka, S; Arumugaswami, V; Vangeloff, AD; Heaton, NS; Sahasrabudhe, S; Randall, G; Sun, R; LaCount, DJ
Published in: Mol Biosyst
December 2013

Hepatitis C virus (HCV) alters the global behavior of the host cell to create an environment conducive to its own replication, but much remains unknown about how HCV proteins elicit these changes. Thus, a better understanding of the interface between the virus and host cell is required. Here we report the results of a large-scale yeast two-hybrid screen to identify protein-protein interactions between HCV genotype 2a (strain JFH1) and cellular factors. Our study identified 112 unique interactions between 7 HCV and 94 human proteins, over 40% of which have been linked to HCV infection by other studies. These interactions develop a more complete picture of HCV infection, providing insight into HCV manipulation of pathways, such as lipid and cholesterol metabolism, that were previously linked to HCV infection and implicating novel targets within microtubule-organizing centers, the complement system and cell cycle regulatory machinery. In an effort to understand the relationship between HCV and related viruses, we compared the HCV 2a interactome to those of other HCV genotypes and to the related dengue virus. Greater overlap was observed between HCV and dengue virus targets than between HCV genotypes, demonstrating the value of parallel screening approaches when comparing virus-host cell interactomes. Using siRNAs to inhibit expression of cellular proteins, we found that five of the ten shared targets tested (CUL7, PCM1, RILPL2, RNASET2, and TCF7L2) were required for replication of both HCV and dengue virus. These shared interactions provide insight into common features of the viral life cycles of the family Flaviviridae.

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Published In

Mol Biosyst

DOI

EISSN

1742-2051

Publication Date

December 2013

Volume

9

Issue

12

Start / End Page

3199 / 3209

Location

England

Related Subject Headings

  • Virus Replication
  • Viral Proteins
  • Two-Hybrid System Techniques
  • RNA, Small Interfering
  • Protein Binding
  • Liver
  • Lipid Metabolism
  • Humans
  • Host-Pathogen Interactions
  • Hepatitis C
 

Citation

APA
Chicago
ICMJE
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Dolan, P. T., Zhang, C., Khadka, S., Arumugaswami, V., Vangeloff, A. D., Heaton, N. S., … LaCount, D. J. (2013). Identification and comparative analysis of hepatitis C virus-host cell protein interactions. Mol Biosyst, 9(12), 3199–3209. https://doi.org/10.1039/c3mb70343f
Dolan, Patrick T., Chaoying Zhang, Sudip Khadka, Vaithilingaraja Arumugaswami, Abbey D. Vangeloff, Nicholas S. Heaton, Sudhir Sahasrabudhe, Glenn Randall, Ren Sun, and Douglas J. LaCount. “Identification and comparative analysis of hepatitis C virus-host cell protein interactions.Mol Biosyst 9, no. 12 (December 2013): 3199–3209. https://doi.org/10.1039/c3mb70343f.
Dolan PT, Zhang C, Khadka S, Arumugaswami V, Vangeloff AD, Heaton NS, et al. Identification and comparative analysis of hepatitis C virus-host cell protein interactions. Mol Biosyst. 2013 Dec;9(12):3199–209.
Dolan, Patrick T., et al. “Identification and comparative analysis of hepatitis C virus-host cell protein interactions.Mol Biosyst, vol. 9, no. 12, Dec. 2013, pp. 3199–209. Pubmed, doi:10.1039/c3mb70343f.
Dolan PT, Zhang C, Khadka S, Arumugaswami V, Vangeloff AD, Heaton NS, Sahasrabudhe S, Randall G, Sun R, LaCount DJ. Identification and comparative analysis of hepatitis C virus-host cell protein interactions. Mol Biosyst. 2013 Dec;9(12):3199–3209.
Journal cover image

Published In

Mol Biosyst

DOI

EISSN

1742-2051

Publication Date

December 2013

Volume

9

Issue

12

Start / End Page

3199 / 3209

Location

England

Related Subject Headings

  • Virus Replication
  • Viral Proteins
  • Two-Hybrid System Techniques
  • RNA, Small Interfering
  • Protein Binding
  • Liver
  • Lipid Metabolism
  • Humans
  • Host-Pathogen Interactions
  • Hepatitis C