Power-laws in interferon-B mRNA distribution in virus-infected dendritic cells

Area of Science:

• Immunology
• Molecular Biology
• Systems Biology

Background:

• Interferon-beta (IFNB1) is a crucial cytokine in antiviral responses.
• Cell-to-cell variability in gene expression is a common phenomenon in biological systems.
• Understanding IFNB1 regulation is key to comprehending innate immunity.

Purpose of the Study:

• To investigate the distribution of IFNB1 mRNA levels in primary human dendritic cells upon viral infection.
• To explore the underlying mechanisms driving the observed gene expression variability.
• To model the stochastic processes involved in IFNB1 gene regulation.

Main Methods:

• Direct measurement of IFNB1 mRNA in the natural chromatin environment of primary human cells.
• Infection of dendritic cells with Newcastle disease virus and influenza A mutant viruses.
• Analysis of mRNA distribution using power-law statistics.
• Development and validation of a computational model for transcriptional pulsing.

Main Results:

• IFNB1 mRNA levels displayed a power-law distribution (exponent close to -1) in response to Newcastle disease virus, indicating extensive cell-to-cell variability.
• Similar power-law behavior was observed with influenza A mutant viruses, though over a truncated range.
• The proposed model of stochastic complex formation and transcriptional pulsing accurately reproduced the experimental power-law distributions.

Conclusions:

• The extensive variability in IFNB1 mRNA expression is not random but follows a power-law distribution.
• Transcriptional pulsing is a likely mechanism regulating IFNB1 expression in response to natural viral stimuli.
• The findings support a model of stochastic gene regulation involving enhanceosome and preinitiation complex formation.