Human cathelicidin compensates for the role of apolipoproteins in hepatitis C virus infectious particle formation

Francesc Puig-Basagoiti, Takasuke Fukuhara, Tomokazu Tamura, Chikako Ono, Kentaro Uemura, Yukako Kawachi, Satomi Yamamoto, Hiroyuki Mori, Takeshi Kurihara, Toru Okamoto, Hideki Aizaki, Yoshiharu Matsuura

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Exchangeable apolipoproteins (ApoA, -C, and -E) have been shown to redundantly participate in the formation of infectious hepatitis C virus (HCV) particles during the assembly process, although their precise role in the viral life cycle is not well understood. Recently, it was shown that the exogenous expression of only short sequences containing amphipathic α-helices from various apolipoproteins is sufficient to restore the formation of infectious HCV particles in ApoB and ApoE double-gene-knockout Huh7 (BE-KO) cells. In this study, through the expression of a small library of human secretory proteins containing amphipathic α-helix structures, we identified the human cathelicidin antimicrobial peptide (CAMP), the only known member of the cathelicidin family of antimicrobial peptides (AMPs) in humans and expressed mainly in bone marrow and leukocytes. We showed that CAMP is able to rescue HCV infectious particle formation in BE-KO cells. In addition, we revealed that the LL-37 domain in CAMP containing amphipathic α-helices is crucial for the compensation of infectivity in BE-KO cells, and the expression of CAMP in nonhepatic 293T cells expressing claudin 1 and microRNA miR-122 confers complete propagation of HCV. These results suggest the possibility of extrahepatic propagation of HCV in cells with low-level or no expression of apolipoproteins but expressing secretory proteins containing amphipathic α-helices such as CAMP.

Original languageEnglish
Pages (from-to)8464-8477
Number of pages14
JournalJournal of virology
Volume90
Issue number19
DOIs
Publication statusPublished - 2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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