Interleukin-28 (IL-28) is a

cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

that comes in two

isoform A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...

s, IL-28A and IL-28B, and plays a role in immune defense against

virus A virus is a submicroscopic infectious agent that replicates only inside the living Cell (biology), cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are ...

es, including the induction of an "antiviral state" by turning on Mx proteins, 2',5'-oligoadenylate synthetase as well as

ISGF3G Interferon regulatory factor 9 is a protein that in humans is encoded by the ''IRF9'' gene, previously known as ISGF3G. Interactions IRF9 has been shown to interact with STAT2 and STAT1 Signal transducer and activator of transcription 1 (STAT1 ...

(Interferon Stimulated Gene Factor 3). IL-28A and IL-28B belong to the type III

interferon Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten ...

family of cytokines and are highly similar (in

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

sequence) to

IL-29 Interleukin-29 (IL-29) is a cytokine and it belongs to type III interferons group, also termed interferons λ (IFN-λ). IL-29 (alternative name IFNλ1) plays an important role in the immune response against pathogenes and especially against v ...

. Their classification as Interferons is due to their ability to induce an antiviral state, while their additional classification as cytokines is due to their chromosomal location as well as the fact that they are encoded by multiple exons, as opposed to a single exon, as most type-I IFNs are.

Discovery

IL-28 was discovered in 2002 by Zymogenetics using a genomic screening process in which the entire human genome was scanned for putative genes. Once these genes were found, a second scan was performed to look specifically for cytokines. Both IL-28 and IL-29 were found in humans using this type of analysis.

Structure

IL-28

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

s are located near IL-29 on

chromosome 19 Chromosome 19 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 19 spans more than 61.7 million base pairs, the building material of DNA. It is considered the most Gene density, gene-ri ...

in humans. The two isoforms of IL-28 (IL-28A and IL-28B) are 96% homologous. Differences in function between the two forms remains unclear. The receptor for IL-28 is composed of a unique IL-28 Receptor Alpha chain which pairs with the IL-10 Receptor Beta chain, leading many to classify IL-28 as an IL-10-like family member.

Function

IL-28 has also been shown to play a role in the adaptive immune response, as its inclusion as an immunoadjuvant during small animal vaccination lead to augmented antigen-specific Interferon Gamma release as well as an increased cytotoxic potential in CD8+ T cells.

Clinical significance

Addition of IL-28 to vaccination results in 100% protection from a lethal H1N1 Influenza challenge in a small animal model when it was paired with an Influenza vaccine that protected only 50% of the time without IL-28. Studies of IL-28B in non-human primate models of vaccination confirmed the small animal models, leading to an increase in Interferon Gamma production and CD8+ T cell activity in the form of cytotoxicity in an HIV vaccine study. Scientists have credited this link to explain why some people infected with HSV-1 experience cold sores, while others do not. A single nucleotide polymorphism (SNP) near the IL28B gene predicts response to

hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection period, people often have mild or no symptoms. Early symptoms can include ...

treatment with

and

ribavirin Ribavirin, also known as tribavirin, is an antiviral medication used to treat illness caused by respiratory syncytial virus (RSV) and hepatitis C virus (HCV) infections, as well as some viral hemorrhagic fevers. For HCV, it is used in combi ...

. The SNP was identified in a

genome-wide association study In genomics, a genome-wide association study (GWA study, or GWAS), is an observational study of a genome-wide set of Single-nucleotide polymorphism, genetic variants in different individuals to see if any variant is associated with a trait. GWA s ...

(GWAS) and is to date the best example of a successful GWAS hit that is clinically relevant.

References

{{Interleukin receptor modulators Interleukins