Hepatitis C virus envelope-mediated entry process (HCV entry)

The Hepatitis C virus (HCV) envelope-mediated entry process is a complex, multi-step mechanism essential for the initiation of viral infection in hepatocytes (Source: PubMed PMID: 23346081). This process is primarily driven by the viral envelope glycoproteins, E1 and E2, which form a non-covalent heterodimer on the virion surface (Source: UniProt P26664). Entry involves a coordinated interaction with several host cell surface factors, including CD81, scavenger receptor class B type I (SR-BI), claudin-1 (CLDN1), and occludin (OCLN) (Source: PubMed PMID: 18328401). Following initial attachment, the virus is internalized via clathrin-mediated endocytosis, where the acidic environment of the endosome triggers a conformational change in the E1/E2 complex to facilitate membrane fusion (Source: PubMed PMID: 15908945). As a therapeutic target, inhibiting this process aims to block the very first stage of the viral life cycle, preventing the establishment of infection and the spread of the virus to healthy cells. Pharmacological strategies include the use of monoclonal antibodies targeting E2 or host receptors, as well as small molecule inhibitors like ITX-5061 that antagonize SR-BI (Source: PubMed PMID: 21412131). Although direct-acting antivirals (DAAs) targeting replication are the current standard of care, entry inhibitors remain a significant area of research for preventing graft reinfection in liver transplant patients (Source: PubMed PMID: 22561025). Challenges in targeting this process include the high genetic diversity of HCV and the potential for the virus to utilize alternative entry pathways or escape mutations (Source: PubMed PMID: 21146482).

Other names

HCV entryHCV cell entryHCV fusionHCV attachmentHCV E1/E2-mediated entry

Inhibition of viral attachment to host cell receptors, blocking of viral-cell membrane fusion, or antagonism of essential host entry factors such as CD81, SR-BI, Claudin-1, and Occludin (Source: PubMed PMID: 23346081).