Abstract
The cluster of differentiation 36 (CD36) is a membrane protein related to lipid metabolism. We show that HCV infection in vitro increased CD36 expression in either surface or soluble form. HCV attachment was facilitated through a direct interaction between CD36 and HCV E1 protein, causing enhanced entry and replication. The HCV co-receptor effect of CD36 was independent of that of SR-BI. CD36 monoclonal antibodies neutralized the effect of CD36 and reduced HCV replication. CD36 inhibitor sulfo-N-succinimidyl oleate (SSO), which directly bound CD36 but not SR-BI, significantly interrupted HCV entry, and therefore inhibited HCV replication. SSO's antiviral effect was seen only in HCV but not in other viruses. SSO in combination with known anti-HCV drugs showed additional inhibition against HCV. SSO was considerably safe in mice. Conclusively, CD36 interacts with HCV E1 and might be a co-receptor specific for HCV entry; thus, CD36 could be a potential drug target against HCV.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Neutralizing / pharmacology
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Antiviral Agents / pharmacology*
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CD36 Antigens / antagonists & inhibitors
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CD36 Antigens / genetics*
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CD36 Antigens / metabolism
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Cell Line, Tumor
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Drug Synergism
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Gene Expression Regulation
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HEK293 Cells
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Hepacivirus / drug effects*
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Hepacivirus / genetics
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Hepacivirus / metabolism
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Hepatocytes / drug effects
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Hepatocytes / pathology
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Hepatocytes / virology
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Host-Pathogen Interactions
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Humans
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Mice
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Oleic Acids / pharmacology*
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Oligopeptides / pharmacology
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Receptors, Virus / antagonists & inhibitors
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Receptors, Virus / genetics*
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Receptors, Virus / metabolism
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Scavenger Receptors, Class B / genetics
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Scavenger Receptors, Class B / metabolism
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Signal Transduction
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Succinimides / pharmacology*
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Toxicity Tests, Acute
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Transgenes
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Viral Envelope Proteins / genetics
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Viral Envelope Proteins / metabolism
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Virus Attachment / drug effects*
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Virus Internalization / drug effects*
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Virus Replication
Substances
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Antibodies, Neutralizing
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Antiviral Agents
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CD36 Antigens
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E1 protein, Hepatitis C virus
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Oleic Acids
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Oligopeptides
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RNA, Small Interfering
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Receptors, Virus
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SCARB1 protein, human
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Scavenger Receptors, Class B
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Succinimides
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Viral Envelope Proteins
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sulfo-N-succinimidyl oleate
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telaprevir