Related Experiment Video
Updated: Aug 3, 2026
In situ Subcellular Fractionation of Adherent and Non-adherent Mammalian Cells
Published on: July 24, 2010
Microarray analysis identifies interferon-inducible genes and Stat-1 as major transcriptional targets of human
1Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Abstract:
Human papillomaviruses (HPVs) infect keratinocytes and induce proliferative lesions. In infected cells, viral gene products alter the activities of cellular proteins, such as Rb and p53, resulting in altered cell cycle response. It is likely that HPV gene products also alter expression of cellular genes. In this study we used microarray analysis to examine the global changes in gene expression induced by high-risk HPV type 31 (HPV31). Among 7,075 known genes and ESTs (expressed sequence tags) tested, we found that 178 were upregulated and 150 were downregulated twofold or more in HPV31 cells compared to normal human keratinocytes. While no specific pattern could be deduced from the list of genes that were upregulated, downregulated genes could be classified to three groups: genes that are involved in the regulation of cell growth, genes that are specifically expressed in keratinocytes, and genes whose expression is increased in response to interferon stimulation. The basal level of expression of several interferon-responsive genes was found to be downregulated in HPV31 cells by both microarray analysis and Northern blot analysis in different HPV31 cell lines. When cells were treated with alpha or gamma interferon, expression of interferon-inducible genes was impaired. At high doses of interferon, the effects were less pronounced. Among the genes repressed by HPV31 was the signal transducer and activator of transcription (Stat-1), which plays a major role in mediating the interferon response. Suppression of Stat-1 expression may contribute to a suppressed response to interferon as well as immune evasion.
Insights
High-risk human papillomaviruses (HPVs) alter cellular gene expression, downregulating interferon-responsive genes and impairing immune responses. This suppression, particularly of Stat-1, may facilitate immune evasion by HPV-infected cells.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Human papillomaviruses (HPVs) are known to disrupt cellular processes by altering protein activities, like Rb and p53, affecting cell cycle regulation.
- It is hypothesized that HPV gene products also influence the expression of cellular genes, contributing to viral pathogenesis.
Purpose of the Study:
- To investigate the global changes in gene expression induced by high-risk HPV type 31 (HPV31) in human keratinocytes.
- To identify specific cellular genes and pathways affected by HPV31 infection.
Main Methods:
- Microarray analysis was employed to compare gene expression profiles between HPV31-infected keratinocytes and normal human keratinocytes.
- Northern blot analysis was used to validate the expression changes of specific interferon-responsive genes.
Main Results:
- HPV31 infection led to significant alterations in gene expression, with 178 genes upregulated and 150 genes downregulated (twofold or more) among 7,075 tested.
- Downregulated genes were primarily involved in cell growth regulation, keratinocyte-specific functions, and interferon response pathways.
- HPV31 suppressed the basal expression of interferon-responsive genes and impaired their induction by interferon (IFN-α and IFN-γ).
- The signal transducer and activator of transcription (Stat-1), crucial for interferon signaling, was found to be repressed by HPV31.
Conclusions:
- High-risk HPV31 significantly alters cellular gene expression in keratinocytes.
- HPV31-mediated suppression of interferon-responsive genes, including Stat-1, likely contributes to impaired cellular immunity and immune evasion.
- Understanding these molecular mechanisms is crucial for developing therapeutic strategies against HPV infections.
More Related Videos
13:41Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus
Published on: March 8, 2012
10:00High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
Published on: March 24, 2015
Related Concept Videos
01:30Inhibitors of Viral Protein Synthesis
01:25Inhibitors Of Virion Release
01:19Inhibitors of Virion Maturation and Assembly