Hepatitis C virus entry (HCV entry)

Hepatitis C virus (HCV) entry is a complex, multi-step process by which the virus attaches to and penetrates host hepatocytes. This process involves the interaction of viral envelope glycoproteins E1 and E2 with several host cell surface factors, including scavenger receptor class B type I (SR-BI), the tetraspanin CD81, and the tight junction proteins claudin-1 (CLDN1) and occludin (OCLN) (Zeisel et al., 2013; Pileri et al., 1998; Evans et al., 2007). Following attachment and receptor-mediated endocytosis, the viral envelope fuses with the endosomal membrane to release the viral genome into the cytoplasm (Lindenbach & Rice, 2005). Targeting HCV entry represents a therapeutic strategy to prevent primary infection, particularly in settings like liver transplantation, or to complement existing direct-acting antivirals (DAAs) (Lupberger et al., 2011). While most current treatments target viral enzymes such as NS3/4A or NS5A, entry inhibitors offer a distinct mechanism of action by blocking the very first stage of the viral lifecycle (Syder et al., 2011). Small molecules like ITX-5061 and repurposed drugs like Ezetimibe have been investigated for their ability to disrupt these critical host-virus interactions (Sainz et al., 2012; Syder et al., 2011).

Other names

HCV cell entryHepatitis C virus infection pathwayHCV attachment and entryHCV internalization

Inhibition of viral attachment to host cells, blockade of interactions with host entry factors (CD81, SR-BI, CLDN1, OCLN), and prevention of pH-dependent membrane fusion (Zeisel et al., 2013; Lindenbach & Rice, 2005).