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The impact of the interferon-lambda family on the innate and adaptive immune response to viral infections.

Egli A, Santer DM, O'Shea D, Tyrrell DL, Houghton M - Emerg Microbes Infect (2014)

Bottom Line: Common single nucleotide polymorphisms (SNPs) in the IFNL3, IFNL4 and the IFNL receptor α-subunit genes have been strongly associated with IFN-α-based treatment of chronic hepatitis C virus infection.It has been demonstrated that IFNL increase Th1- and reduce Th2-cytokines.In turn, this may influence the subsequent priming of cytotoxic T cells versus antibody-secreting B cells, with implications for the breadth and durability of the host response.

View Article: PubMed Central - PubMed

Affiliation: Infection Biology, Department of Biomedicine, University Hospital of Basel , 4031 Basel, Switzerland ; Clinical Microbiology, University Hospital of Basel , 4031 Basel, Switzerland.

ABSTRACT
Type-III interferons (IFN-λ, IFNL) are the most recently described family of IFNs. This family of innate cytokines are increasingly being ascribed pivotal roles in host-pathogen interactions. Herein, we will review the accumulating evidence detailing the immune biology of IFNL during viral infection, and the implications of this novel information on means to advance the development of therapies and vaccines against existing and emerging pathogens. IFNLs exert antiviral effects via induction of IFN-stimulated genes. Common single nucleotide polymorphisms (SNPs) in the IFNL3, IFNL4 and the IFNL receptor α-subunit genes have been strongly associated with IFN-α-based treatment of chronic hepatitis C virus infection. The clinical impact of these SNPs may be dependent on the status of viral infection (acute or chronic) and the potential to develop viral resistance. Another important function of IFNLs is macrophage and dendritic cell polarization, which prime helper T-cell activation and proliferation. It has been demonstrated that IFNL increase Th1- and reduce Th2-cytokines. Therefore, can such SNPs affect the IFNL signaling and thereby modulate the Th1/Th2 balance during infection? In turn, this may influence the subsequent priming of cytotoxic T cells versus antibody-secreting B cells, with implications for the breadth and durability of the host response.

No MeSH data available.


Related in: MedlinePlus

Hypothesis of IFNL3 single nucleotide polymorphism and impact on virus replication. The left panel shows a major allele genotype with a presumed fully functional IFNL3 expression during virus replication. The right shows a minor allele genotype with reduced IFNL3 expression, but increased IFNL4 expression. The genotype results in a significantly different ISG background expression which may be an advantage or disadvantage for different viruses.
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fig3: Hypothesis of IFNL3 single nucleotide polymorphism and impact on virus replication. The left panel shows a major allele genotype with a presumed fully functional IFNL3 expression during virus replication. The right shows a minor allele genotype with reduced IFNL3 expression, but increased IFNL4 expression. The genotype results in a significantly different ISG background expression which may be an advantage or disadvantage for different viruses.

Mentions: Figure 3 illustrates a proposed hypothesis regarding the feedback mechanism between IFN-α and IFNL3/4 according to specific genotypic backgrounds and in response to differing infection scenarios; acute and chronic viral infection (Figure 3). During acute viral infection, the expression of both IFN-α and IFNLs is triggered. In the context of a major allele IFNL3 genotype, IFNL3 is highly expressed and may better inhibit the initial replication of a virus due to a longer lasting anti-viral effect of induced ISGs. This may culminate in virological control and ultimately affect spontaneous clearance of virus. Clearly such outcomes will be reliant on efficient virus-specific T-cell priming, where a key role for IFNL is also proposed.


The impact of the interferon-lambda family on the innate and adaptive immune response to viral infections.

Egli A, Santer DM, O'Shea D, Tyrrell DL, Houghton M - Emerg Microbes Infect (2014)

Hypothesis of IFNL3 single nucleotide polymorphism and impact on virus replication. The left panel shows a major allele genotype with a presumed fully functional IFNL3 expression during virus replication. The right shows a minor allele genotype with reduced IFNL3 expression, but increased IFNL4 expression. The genotype results in a significantly different ISG background expression which may be an advantage or disadvantage for different viruses.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126180&req=5

fig3: Hypothesis of IFNL3 single nucleotide polymorphism and impact on virus replication. The left panel shows a major allele genotype with a presumed fully functional IFNL3 expression during virus replication. The right shows a minor allele genotype with reduced IFNL3 expression, but increased IFNL4 expression. The genotype results in a significantly different ISG background expression which may be an advantage or disadvantage for different viruses.
Mentions: Figure 3 illustrates a proposed hypothesis regarding the feedback mechanism between IFN-α and IFNL3/4 according to specific genotypic backgrounds and in response to differing infection scenarios; acute and chronic viral infection (Figure 3). During acute viral infection, the expression of both IFN-α and IFNLs is triggered. In the context of a major allele IFNL3 genotype, IFNL3 is highly expressed and may better inhibit the initial replication of a virus due to a longer lasting anti-viral effect of induced ISGs. This may culminate in virological control and ultimately affect spontaneous clearance of virus. Clearly such outcomes will be reliant on efficient virus-specific T-cell priming, where a key role for IFNL is also proposed.

Bottom Line: Common single nucleotide polymorphisms (SNPs) in the IFNL3, IFNL4 and the IFNL receptor α-subunit genes have been strongly associated with IFN-α-based treatment of chronic hepatitis C virus infection.It has been demonstrated that IFNL increase Th1- and reduce Th2-cytokines.In turn, this may influence the subsequent priming of cytotoxic T cells versus antibody-secreting B cells, with implications for the breadth and durability of the host response.

View Article: PubMed Central - PubMed

Affiliation: Infection Biology, Department of Biomedicine, University Hospital of Basel , 4031 Basel, Switzerland ; Clinical Microbiology, University Hospital of Basel , 4031 Basel, Switzerland.

ABSTRACT
Type-III interferons (IFN-λ, IFNL) are the most recently described family of IFNs. This family of innate cytokines are increasingly being ascribed pivotal roles in host-pathogen interactions. Herein, we will review the accumulating evidence detailing the immune biology of IFNL during viral infection, and the implications of this novel information on means to advance the development of therapies and vaccines against existing and emerging pathogens. IFNLs exert antiviral effects via induction of IFN-stimulated genes. Common single nucleotide polymorphisms (SNPs) in the IFNL3, IFNL4 and the IFNL receptor α-subunit genes have been strongly associated with IFN-α-based treatment of chronic hepatitis C virus infection. The clinical impact of these SNPs may be dependent on the status of viral infection (acute or chronic) and the potential to develop viral resistance. Another important function of IFNLs is macrophage and dendritic cell polarization, which prime helper T-cell activation and proliferation. It has been demonstrated that IFNL increase Th1- and reduce Th2-cytokines. Therefore, can such SNPs affect the IFNL signaling and thereby modulate the Th1/Th2 balance during infection? In turn, this may influence the subsequent priming of cytotoxic T cells versus antibody-secreting B cells, with implications for the breadth and durability of the host response.

No MeSH data available.


Related in: MedlinePlus