Unlabelled: 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.
Importance: Various exchangeable apolipoproteins play a pivotal role in the formation of infectious HCV during the assembly of viral particles, and amphipathic α-helix motifs in the apolipoproteins have been shown to be a key factor. To the best of our knowledge, we have identified for the first time the human cathelicidin CAMP as a cellular protein that can compensate for the role of apolipoproteins in the life cycle of HCV. We have also identified the domain in CAMP that contains amphipathic α-helices crucial for compensation and show that the expression of CAMP in nonhepatic cells expressing claudin 1 and miR-122 confers complete propagation of HCV. We speculate that low levels of HCV propagation might be possible in extrahepatic tissues expressing secretory proteins containing amphipathic α-helices without the expression of apolipoproteins.
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http://dx.doi.org/10.1128/JVI.00471-16 | DOI Listing |
Eur J Med Chem
January 2025
Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, No. 1 Xian Nong Tan Street, Beijing, 100050, PR China; Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066, Lanzhou University, Lanzhou, 730000, PR China; Institute of Pharmaceutics, School of Pharmacy, 2019RU066, Lanzhou University, Lanzhou, 730000, PR China. Electronic address:
De novo design of antimicrobial peptides is a pivotal strategy for developing new antibacterial agents, leveraging its rapid and efficient nature. (XXYY), where X represents cationic residues, Y denotes hydrophobic residues, and n varies from 2 to 4, is a classical α-helix template. Based on which, numerous antimicrobial peptides have been synthesized.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
A. N. Belozersky Institute of Physico-Chemical Biology, M. V. Lomonosov Moscow State University, Leninskie Gory 1, Bld. 40, Moscow 119992, Russia.
Artificial peptides P4, A1 and A4 are homologous to amphipathic α-helical fragments of the influenza virus M1 protein. P4 and A4 contain the cholesterol recognition sequence CARC, which is absent in A1. As shown previously, P4 and A4 but not A1 have cytotoxic effects on some eukaryotic and bacterial cells.
View Article and Find Full Text PDFAntibiotics (Basel)
January 2025
Departamento de Química, Faculdade de Ciências Exatas, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Campus JK, Diamantina 39100-000, MG, Brazil.
This study investigates the structural and biophysical properties of the wild-type antimicrobial peptide LyeTx I, isolated from the venom of the spider , and its analog LyeTx I-b, designed to enhance antibacterial activity, selectivity, and membrane interactions by the acetylation and increased amphipathicty. : To understand the mechanisms behind these enhanced properties, comparative analyses of the structural, topological, biophysical, and thermodynamic aspects of the interactions between each peptide and phospholipid bilayers were evaluated. Both peptides were isotopically labeled with H-Ala and N-Leu to facilitate structural studies via NMR spectroscopy.
View Article and Find Full Text PDFAntibiotics (Basel)
December 2024
Czech Advanced Technology and Research Institute (CATRIN), Palacký University Olomouc, 77900 Olomouc, Czech Republic.
Cathelicidins are a group of cationic, amphipathic peptides that play a vital role in the innate immune response of many vertebrates, including humans. Produced by immune and epithelial cells, they serve as natural defenses against a wide range of pathogens, including bacteria, viruses, and fungi. In humans, the cathelicidin LL-37 is essential for wound healing, maintaining skin barrier integrity, and combating infections.
View Article and Find Full Text PDFToxins (Basel)
January 2025
Department of Experimental Pathology, Federal University of São João del-Rei, Divinópolis 36301-158, Brazil.
The discovery of novel cytotoxic drugs is of paramount importance in contemporary medical research, particularly in the search for treatments with fewer side effects and higher specificity. Antimicrobial peptides are an interesting class of molecules for this endeavor. In this context, the LyeTx III, a new peptide extracted from the venom of the spider, stands out.
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