The low-density lipoprotein receptor LDLR mediates cellular entry of nonenveloped hepatitis A virus - PubMed
4 hours ago
- #viral endocytosis
- #LDLR receptor
- #Hepatitis A virus entry
- LDLR (low-density lipoprotein receptor) facilitates cellular entry of nonenveloped hepatitis A virus (nHAV), but not quasi-enveloped particles (eHAV).
- The receptor's function in nHAV uptake is clathrin-dependent and occurs without altering viral attachment, with binding optimal above pH7 and not destabilizing the capsid.
- Cryo-EM structure shows LDLR interacts with VP1 at the capsid's fivefold vertex, though binding appears flexible or asymmetrical, and ganglioside GD1a binds a similar region.
- LDLR knockout cells show restricted nHAV entry, which is restored by full-length LDLR but not mutants lacking specific domains, implicating other LDLR family members may also assist.
- Inhibitors like soluble LDLR ectodomain, anti-LDLR antibodies, and recombinant chaperone protein block nHAV entry, highlighting LDLR's role in shuttling nHAV to endolysosomes for ganglioside binding.