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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
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Interferon lambda 4 expression is suppressed by the host during viral infection.
MeeAe Hong1, Johannes Schwerk1, Chrissie Lim1
1Department of Immunology, University of Washington, Seattle, WA 98109.
The Journal of Experimental Medicine
|November 2, 2016
Summary
Humans suppress the expression of interferon lambda 4 (IFNλ4), a recently discovered antiviral protein. This suppression occurs through multiple mechanisms, limiting functional IFNλ4 and suggesting reliance on other interferon lambda family members for immune responses.
Area of Science:
- Immunology
- Virology
- Molecular Biology
Background:
- Interferon (IFN) lambdas are key antiviral proteins, particularly in liver and mucosal infections.
- While IFNλ1, IFNλ2, and IFNλ3 possess antiviral properties, the recently identified IFNL4 gene's role in hepatitis C virus (HCV) infection is detrimental, though the mechanism remains unclear.
- A notable feature of human IFNL4 is a genetic variant causing a premature stop codon.
Purpose of the Study:
- To conduct a molecular and biochemical characterization of IFNλ4.
- To elucidate the role and regulatory mechanisms of IFNλ4 expression.
- To understand why IFNL4 expression is detrimental to HCV infection.
Main Methods:
- Molecular and biochemical characterization of IFNλ4.
- Analysis of splice variants and protein isoforms.
- Investigation of mRNA translation efficiency, including polyribosome loading and polyadenylation signals.
Main Results:
- IFNλ4 demonstrates antiviral activity comparable to IFNλ3 without adverse effects on other antiviral IFN activities or cell viability.
- Humans employ multiple strategies to restrict functional IFNλ4 expression, utilizing noncoding splice variants and nonfunctional protein isoforms.
- Protein-coding IFNL4 mRNA exhibits poor translation efficiency due to lack of polyribosome loading and a weak polyadenylation signal.
Conclusions:
- Human cells actively suppress the expression of functional IFNλ4.
- The observed suppression mechanisms suggest that the immune system relies on other interferon lambda family members for effective antiviral defense.
- Understanding IFNλ4 regulation provides insight into host-virus interactions and immune evasion strategies.
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