Skip to main content
An official website of the United States government
Government Funding Lapse
Because of a lapse in government funding, the information on this website may not be up to date, transactions submitted via the website may not be processed, and the agency may not be able to respond to inquiries until appropriations are enacted.

The NIH Clinical Center (the research hospital of NIH) is open. For more details about its operating status, please visit cc.nih.gov.

Updates regarding government operating status and resumption of normal operations can be found at opm.gov.

Interferon Lambda 4 Phenotypes

A collaboration led by DCEG investigators in the Infections and Immunoepidemiology Branch (IIB) and the Laboratory of Translational Genomics (LTG) led to the discovery of the interferon lambda 4 (IFNL4) gene (Prokunina-Olsson L, Muchmore B, Tang W, et al. A variant upstream of IFNL3 (IL28B) creating a new interferon gene IFNL4 is associated with impaired clearance of hepatitis C virus. Nat Genet 2013). Recent epidemiological studies have associated IFNL4 genotype with hepatic inflammation and fibrosis, which are precursors of hepatocellular carcinoma (HCC), as well as mucinous ovarian carcinoma, a rare cancer subtype of uncertain etiology. Evidence of strong evolutionary selection against the IFNL4-ΔG allele suggests IFNL4 could impact diseases besides HCV infection; recent studies in mice demonstrated that the interferon lambda family plays an important role in a wide range of infections. Taken together, these findings make IFNL4 a candidate gene for many infections and conditions. Recently, IIB investigators and their colleagues reported results from a study in which they examined the possible relationship between IFNL4 genotype and 16 opportunistic infections or malignancies in a large cohort of men who have sex with men and who were infected with human immunodeficiency virus type 1 (Fang MZ, Jackson SS, Pfeiffer RM, et al. No association of IFNL4 genotype with opportunistic infections and cancers among men with HIV-1 infection. Clin Infect Dis 2022).

IIB researchers have initiated additional investigations to examine the phenotypic range of the IFNL4 genotype, including a study of hepatic inflammation and fibrosis, which are precursors of hepatocellular carcinoma, and a phenome-wide association study for the IFNL4 genotype among patients enrolled in a large managed care organization.

For more information, contact Thomas O’Brien.
Infections and Immunoepidemiology Branch - Research Areas

Email