Abstract
Hepatitis C virus (HCV) infection is a major worldwide health problem which can cause chronic hepatitis, liver fibrosis and hepatocellular carcinoma (HCC). There is still no vaccine to prevent HCV infection. Currently, the clinical treatment of HCV infection mainly relies on the use of direct-acting antivirals (DAAs) which are expensive and have side effects. Here, BmKDfsin3, a scorpion defensin from the venom of Mesobuthus martensii Karsch, is found to dose-dependently inhibit HCV infection at noncytotoxic concentrations and affect viral attachment and post-entry in HCV life cycle. Further experimental results show that BmKDfsin3 not only suppresses p38 mitogen-activated protein kinase (MAPK) activation of HCV-infected Huh7.5.1 cells, but also inhibits p38 activation of Huh7.5.1 cells stimulated by tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) or lipopolysaccharide (LPS). BmKDfsin3 is also revealed to enter into cells. Using an upstream MyD88 dimerization inhibitor ST2345 or kinase IRAK-1/4 inhibitor I, the inhibition of p38 activation represses HCV replication in vitro. Taken together, a scorpion defensin BmKDfsin3 inhibits HCV replication, related to regulated p38 MAPK activation.
Highlights
Defensin is a class of cationic peptides rich in disulfide bonds and widely distributed in fungi, plants and animals, and is an important part of the defense system [1]
We found that BmKDfsin3 can inhibit Hepatitis C virus (HCV) replication and affect the attachment and post-entry stages of the viral infection cycle at noncytotoxic concentrations
BmKDfsin3 is a scorpion defensin characterized in the M. martensii genome [28]
Summary
Defensin is a class of cationic peptides rich in disulfide bonds and widely distributed in fungi, plants and animals, and is an important part of the defense system [1]. BmKDfsin derived from the venom of the scorpion Mesobuthus martensii Karsch was reported to inhibit hepatitis B virus (HBV) replication by our group [12]. We ask whether the scorpion defensin BmKDfsin affects viral replication and regulates virus-induced p38 activation. BmKDfsin, a scorpion defensin derived from M. martensii Karsch contains 38 amino acid residues, which includes six cysteine residues forming three pairs of disulfide bonds. We found that BmKDfsin can inhibit HCV replication and affect the attachment and post-entry stages of the viral infection cycle at noncytotoxic concentrations. Inhibiting the p38 MAPK signal pathway by using the MyD88 dimerization inhibitor and IRAK inhibitor can suppress HCV replication. BmKDfsin inhibits HCV replication, which is related to the classical p38 MAPK signal pathway
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
