• Abstract
• Full-Text PDF [1896 KB]
• Full-Text XML
• Article Versions Notes
• Supplement File 1
• Supplement File 2

• Article Statistics
• PubMed/Medline
• Google Scholar
• Order Reprints

• Cite this article
• Export to BibTeX
• Export to EndNote

• [+] on DOAJ
• Papic, N
• Maxwell, C
• Delker, D
• Liu, S
• Heale, B
• Hagedorn, C
• [+] on Google Scholar
• Papic, N
• Maxwell, C
• Delker, D
• Liu, S
• Heale, B
• Hagedorn, C
• [+] on PubMed
• Papic, N
• Maxwell, C
• Delker, D
• Liu, S
• Heale, B
• Hagedorn, C

•  CiteULike
•  Facebook
•  Mendeley
•  Twitter

This article is

• freely available
• re-usable

Viruses 2012, 4(4), 581-612; doi:10.3390/v4040581

Article

RNA-Sequencing Analysis of 5' Capped RNAs Identifies Many New Differentially Expressed Genes in Acute Hepatitis C Virus Infection

Neven Papic ^1,† , Christopher I. Maxwell ^1,2,† , Don A. Delker ¹ , Shuanghu Liu ¹ , Bret S. E. Heale ¹  and Curt H. Hagedorn ^1,3,*

¹ Department of Medicine, University of Utah, 30 N 1900 E #3C310, Salt Lake City, UT 84132, USA ² Huntsman Cancer Institute, University of Utah, 30 N 1900 E #3C310, Salt Lake City, UT 84132, USA ³ Department of Experimental Pathology, University of Utah, 30 N 1900 E #3C310, Salt Lake City, UT 84132, USA ^† These authors contributed equally to this work.

* Author to whom correspondence should be addressed.

Received: 7 February 2012; in revised form: 31 March 2012 / Accepted: 3 April 2012 / Published: 16 April 2012

(This article belongs to the Special Issue Hepatitis C Pathology)

Download PDF Full-Text [1896 KB, uploaded 24 April 2012 16:08 CEST]

Abstract: We describe the first report of RNA sequencing of 5' capped (Pol II) RNAs isolated from acutely hepatitis C virus (HCV) infected Huh 7.5 cells that provides a general approach to identifying differentially expressed annotated and unannotated genes that participate in viral-host interactions. We identified 100, 684, and 1,844 significantly differentially expressed annotated genes in acutely infected proliferative Huh 7.5 cells at 6, 48, and 72 hours, respectively (fold change ≥ 1.5 and Bonferroni adjusted p-values < 0.05). Most of the differentially expressed genes (>80%) and biological pathways (such as adipocytokine, Notch, Hedgehog and NOD-like receptor signaling) were not identified by previous gene array studies. These genes are critical components of host immune, inflammatory and oncogenic pathways and provide new information regarding changes that may benefit the virus or mediate HCV induced pathology. RNAi knockdown studies of newly identified highly upregulated FUT1 and KLHDC7B genes provide evidence that their gene products regulate and facilitate HCV replication in hepatocytes. Our approach also identified novel Pol II unannotated transcripts that were upregulated. Results further identify new pathways that regulate HCV replication in hepatocytes and suggest that our approach will have general applications in studying viral-host interactions in model systems and clinical biospecimens.

Keywords: HCV; JFH-1; RNA-seq; gene expression; next generation sequencing; 5' cap; Huh 7.5; FUT1; KLHDC7B

Supplementary Files

• Supplementary File 1:

  PDF-Document (PDF, 1210 KB)

• Supplementary File 2:

  XLS-Document (XLS, 484 KB)

Article Statistics

Cite This Article