Genetic Polymorphisms within Interferon-λ Region and Interferon-λ3 in the Human Pathophysiology: Their Contribution to Outcome, Treatment, and Prevention of Infections with Hepatotropic Viruses

Current Medicinal Chemistry
Alicja E Grzegorzewska

Abstract

Genetic polymorphisms within the interferon λ (IFN-λ) chromosomal region, mainly rs12979860 of IFN-λ4 gene (IFNL4), are known as associated with spontaneous hepatitis C virus (HCV) resolution and sustained viral response to therapy with pegylated interferon- α and ribavirin. Strong linkage disequilibrium of IFNL4 rs12979860 with IFNL4 rs368234815, which is casually associated with HCV spontaneous and therapeutical eradication, at least partially explains favorable HCV outcomes attributed to major homozygosity in rs12979860. Effects of IFN-based antiviral treatment are associated with pretreatment expression of the IFN-λ1 receptor, expression of hepatic IFN-stimulated genes, production of IFN- λ4, and preactivation of the JAK-STAT signaling. Nowadays direct-acting antivirals (DAAs) became a potent tool in the treatment of hepatitis C, but IFN-λs are still under investigation as potential antivirals and might be an option in HCV infection (DAA resistance, recurrent viremia, adverse effects). Patients with altered immunocompetence are especially prone to infections. In uremic subjects, polymorphisms within the IFN-λ chromosomal region associate with spontaneous HCV clearance, similarly like in the non-uremic population. Circulatin...Continue Reading

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Citations

Mar 2, 2019·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Ahmad AyadiAbolfazl Fateh
May 26, 2020·Journal of Computational Chemistry·Aijaz Ahmad MalikChanin Nantasenamat

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