한빛사논문
- 조회1,625
Abstract
MeeAe Hong,1* Johannes Schwerk,1* Chrissie Lim,1* Alison Kell,1 Abigail Jarret,1 Joseph Pangallo,1 Yueh.Ming Loo,1 Shuanghu Liu,2 Curt H. Hagedorn,3,4 Michael Gale Jr.,1 and Ram Savan1
1Department of Immunology, University of Washington, Seattle, WA 98109
2Department of Medicinal Chemistry, College of Pharmacy, University of Utah, Salt Lake City, UT 84112
3Department of Medicine and 4Genetics Program, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, AR 72205
Correspondence to Ram Savan
*M. Hong, J. Schwerk, and C. Lim contributed equally to this paper.
Abstract
Interferon (IFN) lambdas are critical antiviral effectors in hepatic and mucosal infections. Although IFNλ1, IFNλ2, and IFNλ3 act antiviral, genetic association studies have shown that expression of the recently discovered IFNL4 is detrimental to hepatitis C virus (HCV) infection through a yet unknown mechanism. Intriguingly, human IFNL4 harbors a genetic variant that introduces a premature stop codon. We performed a molecular and biochemical characterization of IFNλ4 to determine its role and regulation of expression. We found that IFNλ4 exhibits similar antiviral activity to IFNλ3 without negatively affecting antiviral IFN activity or cell survival. We show that humans deploy several mechanisms to limit expression of functional IFNλ4 through noncoding splice variants and nonfunctional protein isoforms. Furthermore, protein-coding IFNL4 mRNA are not loaded onto polyribosomes and lack a strong polyadenylation signal, resulting in poor translation efficiency. This study provides mechanistic evidence that humans suppress IFNλ4 expression, suggesting that immune function is dependent on other IFNL family members.
논문정보
- Research article
- 2016년 10월 (BRIC 등록일 2016-11-08)
- 국외 연구진
댓글 작성 로그인
팝업 닫기관련 링크
