Immunomodulatory Function of Interleukin 28B During Primary Infection With Cytomegalovirus

Egli, Adrian; Levin, Aviad; Santer, Deanna M.; Joyce, Michael; O'Shea, Dàire; Thomas, Bradley; Lisboa, Luiz F.; Barakat, Khaled; Bhat, Rakesh; Fischer, Karl; Houghton, Michael; Tyrrell, D. Lorne; Kumar, Deepali; Humar, Atul

doi:10.1093/infdis/jiu144

Cited by 68 publications

(90 citation statements)

References 47 publications

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“…The minor allele of a further SNP within exon 2, rs117648444, causes an amino acid substitution (P70S), leading to a functionally impaired IFNL4 protein. Transcription of IFNL3 has been shown to be related to rs12979860 [58] and ss469415590 [57], as well as to an SNP within the 3′-UTR which was shown to mediate miRNA-driven mRNA decay [60]. …”

Section: Interferonsmentioning

confidence: 99%

“…Here too, a specific design ensured differentiation between IFNL3 and IFNL2 transcripts. The cohort analyzed by Egli et al [58] was not genotyped for ss469415590. However, as in the Canadian population IL28B/IFNL3 rs12979860 and IFNL4 ss469415590 are in close LD, data might still reflect an association between the IFNL4 ss469415590 TT allele and an increased IFNL3 expression.…”

Section: Further Proposed Roles Of Ifnl Snpsmentioning

confidence: 99%

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Activation of Type I and Type III Interferons in Chronic Hepatitis C

Mihm

2015

J Innate Immun

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Infection with hepatitis C virus (HCV) results in chronic and progressive liver disease. Persistency rates add up to 85%. Despite recognition of the virus by the human host in peripheral blood and in the liver, immune response appears to be ineffective in clearing infection. The ability to spontaneously eradicate the virus as well as the outcome of infection upon therapy with human recombinant interferon-α (IFN-α) was found to correlate most closely with genetic variations within the region encoding the IFN-λ genes, as revealed by genome-wide association studies on main ethnic populations in 2009. This review summarizes the induction of type I and type III IFN genes and their effectors, the IFN-stimulated genes. It focusses on the in vivo situation in chronic HCV infection in man both in the peripheral blood compartment and in the liver. It also addresses the impact of genetic polymorphisms in the region of type III IFN genes on their activation. Finally, it discusses how antiviral drugs (i.e. IFN-α, ribavirin and the direct-acting antivirals) may complementarily control the activation of endogenous IFNs and succeed in combatting infections.

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Section: Interferonsmentioning

confidence: 99%

Section: Further Proposed Roles Of Ifnl Snpsmentioning

confidence: 99%

Activation of Type I and Type III Interferons in Chronic Hepatitis C

Mihm

2015

J Innate Immun

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“…Allo-HSCT recipients that experienced acute GvHD and active CMV infection presented higher frequencies of the genotype T/T of the CD28 molecule. On the contrary, data from Bravo and collaborators seemed to point to a protective effect of the donor homozygous T allele of the IL-28B against CMV infection in allo-HSCT [100], which was supported by the study of Egli et al [101].…”

Section: Gene Polymorphismsmentioning

confidence: 88%

The immune response to cytomegalovirus in allogeneic hematopoietic stem cell transplant recipients

Ciáurriz

Zabalza

Beloki

et al. 2015

Cell. Mol. Life Sci.

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Approximately, up to 70 % of the human population is infected with cytomegalovirus (CMV) that persists for life in a latent state. In healthy people, CMV reactivation induces the expansion of CMV-specific T cells up to 10 % of the entire T cell repertoire. On the contrary, CMV infection is a major opportunistic viral pathogen that remains a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Due to the delayed CMV-specific immune recovery, the incidence of CMV reactivation during post-transplant period is very high. Several methods are currently available for the monitoring of CMV-specific responses that help in clinical monitoring. In this review, essential aspects in the immune recovery against CMV are discussed to improve the better understanding of the immune system relying on CMV infection and, thereby, helping the avoidance of CMV disease or reactivation following hematopoietic stem cell transplantation with severe consequences for the transplanted patients.

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“…Egli et al 47 tested the association of the IFNL SNP rs8099917 with CMV replication in a small number of solid organ transplant patients (n = 38) who were seronegative for CMV (but received an organ transplant from a CMVseropositive donor) and who had stopped receiving antiviral prophylaxis. They found that the minor allele at rs8099917 (G) was associated with decreased CMV replication (P = 0.036) in a dominant model of inheritance.…”

Section: Cytomegalovirus Cytomegalovirus (Cmv) Is a Herpes Virus Thamentioning

confidence: 99%

Gene–disease association with human IFNL locus polymorphisms extends beyond hepatitis C virus infections

Chinnaswamy

2016

Genes Immun

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Interferon (IFN) lambda (IFN-λ or type III IFN) gene polymorphisms were discovered in the year 2009 to have a strong association with spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection in human hosts. This landmark discovery also brought renewed interest in type III IFN biology. After more than half a decade since this discovery, we now have reports that show that genetic association of IFNL gene polymorphisms in humans is not limited only to HCV infections but extends beyond, to include varied diseases such as non-alcoholic fatty liver disease, allergy and several other viral diseases including that caused by the human immunodeficiency virus. Notably, all these conditions have strong involvement of host innate immune responses. After the discovery of a deletion polymorphism that leads to the expression of a functional IFN-λ4 as the prime 'functional' variant, the relevance of other polymorphisms regulating the expression of IFN-λ3 is in doubt. Herein, I seek to critically address these issues and review the current literature to provide a framework to help further understanding of IFN-λ biology.

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Immunomodulatory Function of Interleukin 28B During Primary Infection With Cytomegalovirus

Abstract: We postulate that IL-28B may act as a key regulator of ISG expression during primary CMV infection. IL-28B SNPs may be associated with higher antiviral ISG expression, which results in better replication control.

Cited by 68 publications

References 47 publications

Activation of Type I and Type III Interferons in Chronic Hepatitis C

Activation of Type I and Type III Interferons in Chronic Hepatitis C

The immune response to cytomegalovirus in allogeneic hematopoietic stem cell transplant recipients

Gene–disease association with human IFNL locus polymorphisms extends beyond hepatitis C virus infections

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