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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

1,†
, 1,2,†
, 1
, 1
, 1
 and 1,3,*
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)
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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 HCV; JFH-1; RNA-seq; gene expression; next generation sequencing; 5' cap; Huh 7.5; FUT1; KLHDC7B
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Papic, N.; Maxwell, C.I.; Delker, D.A.; Liu, S.; Heale, B.S.E.; Hagedorn, C.H. RNA-Sequencing Analysis of 5' Capped RNAs Identifies Many New Differentially Expressed Genes in Acute Hepatitis C Virus Infection. Viruses 2012, 4, 581-612.

AMA Style

Papic N, Maxwell CI, Delker DA, Liu S, Heale BSE, Hagedorn CH. RNA-Sequencing Analysis of 5' Capped RNAs Identifies Many New Differentially Expressed Genes in Acute Hepatitis C Virus Infection. Viruses. 2012; 4(4):581-612.

Chicago/Turabian Style

Papic, Neven; Maxwell, Christopher I.; Delker, Don A.; Liu, Shuanghu; Heale, Bret S. E.; Hagedorn, Curt H. 2012. "RNA-Sequencing Analysis of 5' Capped RNAs Identifies Many New Differentially Expressed Genes in Acute Hepatitis C Virus Infection." Viruses 4, no. 4: 581-612.


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