Interferon lambda alleles predict innate antiviral immune responses and hepatitis C virus permissiveness

Timothy Sheahan, Naoko Imanaka, Svetlana Marukian, Marcus Dorner, Peng Liu, Alexander Ploss, Charles M. Rice

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Hepatitis C virus (HCV) infection can result in viral chronicity or clearance. Although host genetics and particularly genetic variation in the interferon lambda (IFNL) locus are associated with spontaneous HCV clearance and treatment success, the mechanisms guiding these clinical outcomes remain unknown. Using a laser capture microdissection-driven unbiased systems virology approach, we isolated and transcriptionally profiled HCV-infected and adjacent primary human hepatocytes (PHHs) approaching single-cell resolution. An innate antiviral immune signature dominated the transcriptional response but differed in magnitude and diversity between HCV-infected and adjacent cells. Molecular signatures associated with more effective antiviral control were determined by comparing donors with high and low infection frequencies. Cells from donors with clinically unfavorable IFNL genotypes were infected at a greater frequency and exhibited dampened antiviral and cell death responses. These data suggest that early virus-host interactions, particularly host genetics and induction of innate immunity, critically determine the outcome of HCV infection.

Original languageEnglish (US)
Pages (from-to)190-202
Number of pages13
JournalCell Host and Microbe
Volume15
Issue number2
DOIs
StatePublished - Feb 12 2014

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Virology

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