Virus attachment to hepatocytes
HBV virion attaches specifically to the hepatocytes, by interacting with several receptors in a manner which is still poorly understood in 2011.
The N-terminal 48 amino acids of the preS1 domain of L protein (in particular amino acids 9 to 15), its myristoylation and the integrity of a region in the antigenic loop of the S domain in the L and/or S protein are essential for the interaction with the target cell receptor and infectivity (De Falco et al. 2001) Rating=2, (Jaoude et al. 2005) Rating=2, (Jaoude et al. 2007) Rating=2, (Blanchet et al. 2007) Rating=2, (Schulze et al. 2010) Rating=2. Indeed infection can be blocked with a myristoylated HBVpre-S1 peptide (amino acids 2-48) and introduction of mutations in the same conserved region of L abrogates infectivity (Engelke et al. 2006) Rating=2. Pre-S2 domain, on the contrary, does not seem to be involved in virus attachment and entry, since it is dispensable for infectivity (Ni et al. 2010) Rating=1.
However, although HBVpre-S1 peptide 2-48 abrogates infectivity, binding to the host target cell is still observed. This leads to the hypothesis that binding and entry into the target cell includes at least two steps, a low-affinity binding to cellular (but not only hepatocyte-specific) receptor, possibly heparin sulfate proteoglycans (HSPG), followed by a high affinity transfer to a hepatocyte-specific receptor that is blocked by acylated peptides in a complex manner (Engelke et al. 2006) Rating=1, (Leistner et al. 2008) Rating=1.
Some studies have shown that the liver-specific asialoglycoprotein receptor interacts specifically with the pre-S1 domain (Yang et al. 2010), (Zhang et al. 2011).
Efficient internalization of HBV virions and subviral particles has been shown within dendritic cells (DCs) although mostly subviral particles were internalized (Vincent et al. 2011).