Virus-Host Cell Interactions during Hepatitis C Virus RNA Replication

Impact of Polyprotein Expression on the Cellular Transcriptome and Cell Cycle Association with Viral RNA Synthesis

Frank Scholle, Kui Li, Francis Bodola, Masanori Ikeda, Bruce A. Luxon, Stanley M. Lemon

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Considerable controversy surrounds the impact of hepatitis C virus (HCV) protein expression on viability of host cells and regulation of the cell cycle. Both promotion of cellular proliferation and apoptosis have been observed in different experimental systems. To determine whether expression of the entire complement of HCV proteins in the context of ongoing viral RNA replication significantly alters the host cell transcriptome and cell cycle regulatory processes, we carried out high-density oligonucleotide microarray studies and analyzed cell cycle distributions and S-phase entry in Huh7 cell clones harboring selectable, full-length, replicating HCV RNAs that express the entire genotype 1b, HCV-N polyprotein, and clonally related cells in which all viral RNA was eliminated by prior treatment with alpha interferon. Oligonucleotide microarray analyses revealed only subtle, coordinated differences in the mRNA profiles of cells containing replicating viral RNA and their interferon-cured progeny, with variation between different cell clones having a greater influence on the cellular transcriptome than the presence or absence of replicating HCV RNA. Flow cytometric analysis demonstrated no significant differences in cell cycle distribution among populations of asynchronously growing cells of both types. Cell lines containing replicating viral RNA and their interferon-cured progeny were able to reenter the cell cycle similarly after transient G1 arrest. In contrast, although viral protein expression and genome replication did not alter cell cycle control in these cells, HCV genome replication was highly dependent on cellular proliferation, with viral RNA synthesis strongly decreased in poorly proliferating, confluent, or serum-starved cells and substantially enhanced in the S phase of the cell cycle.

Original languageEnglish (US)
Pages (from-to)1513-1524
Number of pages12
JournalJournal of Virology
Volume78
Issue number3
DOIs
StatePublished - Feb 1 2004

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Polyproteins
Hepatitis C virus
Viral RNA
Virus Replication
Transcriptome
transcriptome
Cell Communication
Hepacivirus
cell cycle
Cell Cycle
RNA
Viruses
viruses
synthesis
cells
Oligonucleotide Array Sequence Analysis
S Phase
Interferons
Clone Cells
Cell Proliferation

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Virus-Host Cell Interactions during Hepatitis C Virus RNA Replication : Impact of Polyprotein Expression on the Cellular Transcriptome and Cell Cycle Association with Viral RNA Synthesis. / Scholle, Frank; Li, Kui; Bodola, Francis; Ikeda, Masanori; Luxon, Bruce A.; Lemon, Stanley M.

In: Journal of Virology, Vol. 78, No. 3, 01.02.2004, p. 1513-1524.

Research output: Contribution to journalArticle

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