Antimicrobial peptide LL-37 attenuates infection of hepatitis C virus
| Autor: | Masaaki Shiina, Takanobu Kato, Takaji Wakita, Asako Murayama, Shinichi Asabe, Norie Yamada, Michio Imawari, Nao Sugiyama, Takuya Matsumura |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Infectivity Innate immune system Hepatology Hepatitis C virus medicine.medical_treatment virus diseases Biology Antimicrobial medicine.disease_cause Virology digestive system diseases Virus Microbiology Cathelicidin 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Infectious Diseases Cell culture Interferon medicine 030211 gastroenterology & hepatology medicine.drug |
| Zdroj: | Hepatology Research. 46:924-932 |
| ISSN: | 1386-6346 |
| Popis: | Aim Although recent studies indicate that supplementation with vitamin D (VD) potentiates a sustained viral response by interferon-based therapy to chronic hepatitis C, detailed mechanisms are not fully defined. The production of cathelicidin, an antimicrobial peptide, has been demonstrated to be part of the VD-dependent antimicrobial pathway in innate immunity. Cathelicidin is known to directly kill or inhibit the growth of microbial pathogens including mycobacteria and viruses. Methods We used a hepatitis C virus (HCV) cell culture system to clarify the anti-HCV effects of the human cathelicidin, LL-37. HuH-7 cells were administrated with LL-37 and infected with cell culture-generated HCV (HCVcc). HCV propagation was estimated by measuring the level of HCV core antigen (Ag). Results Treatment with LL-37 resulted in decreased intra- and extracellular levels of HCV core Ag, suggesting inhibition of HCV propagation. To assess the effects of LL-37 on HCV replication, JFH-1 subgenomic replicon RNA-transfected cells were treated with LL-37. However, inhibition of HCV replication was not detected by this assay. To clarify the effects on HCV infection, we treated HCVcc with LL-37 and removed the antimicrobial peptide prior to use of the virus in infection. This exposure of HCVcc to LL-37 diminished the infectivity titers in a dose-dependent fashion. Iodixanol density gradient analysis revealed that the peak fraction of infectivity titer was eliminated by LL-37 treatment. Conclusion The VD-associated antimicrobial peptide LL-37 attenuated the infectivity of HCV. This anti-HCV effect of LL-37 may explain the contribution of VD to the improved efficacy of interferon-based therapy. |
| Databáze: | OpenAIRE |
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