Abstract:
:Genetic variants surrounding the interferon-λ3 (IFNL3) gene are strongly associated with clearance of hepatitis C virus (HCV). A variant (rs368234815 TT/ΔG) upstream of IFNL3 was recently implicated to control expression of a novel gene termed IFNL4. We conducted genetic analysis of rs368234815 in a chronic HCV patient cohort and molecular studies of IFNL4 in primary human hepatocytes (PHHs). Analysis of PHHs that are heterozygous at rs368234815 revealed that the IFNL4 transcript isoform is rare, accounting for 2% of transcripts arising from the IFNL4 locus. Nevertheless, IFNL4 over-expression inhibited replication of multiple Flaviviridae and IFNL4 anti-viral potency required the IFNL receptor. In contrast to IFNL3, IFNL4 was inefficiently secreted and appeared to act in a cell-autonomous manner. Genetic analysis revealed associations of rs368234815 with sustained virological response and pre-treatment viral load. The findings suggest that IFNL4 is an atypical IFNL whose activity may be maladaptive to clearance of HCV infection.
journal_name
Virologyjournal_title
Virologyauthors
Lu YF,Goldstein DB,Urban TJ,Bradrick SSdoi
10.1016/j.virol.2014.12.020subject
Has Abstractpub_date
2015-02-01 00:00:00pages
334-340eissn
0042-6822issn
1096-0341pii
S0042-6822(14)00557-1journal_volume
476pub_type
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