Sandbox Reserved 1769: Difference between revisions
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=== Mechanism of HBV/HDV Infection === | === Mechanism of HBV/HDV Infection === | ||
After binding to NTCP in the <scene name='95/952697/Ntcp_open-pore_state/26'>open-pore state</scene>, the viruses remain bound until low bile salt levels in the blood shift equilibria enough that [https://en.wikipedia.org/wiki/Endocytosis endocytosis] of the virus occurs. Once inside the cell, the viral genetic information is released. | After binding to NTCP in the <scene name='95/952697/Ntcp_open-pore_state/26'>open-pore state</scene>, the viruses remain bound until low bile salt levels in the blood shift equilibria enough that [https://en.wikipedia.org/wiki/Endocytosis endocytosis] of the virus occurs. Once inside the cell, the viral genetic information is released. | ||
The exact mechanism of how HBV and HDV bind to NTCP is not certain | The exact mechanism of how HBV and HDV bind to NTCP is not certain, <scene name='95/952696/Residues_84-87_and_157-165_new/1'>two critical sites</scene> on NTCP for HBV/HDV binding have been identified: residues <scene name='95/952696/Residues_84-87_new/1'>84-87</scene> and <scene name='95/952696/Residues_157-165_new/1'>157-165</scene>. An additional [https://en.wikipedia.org/wiki/Single-nucleotide_polymorphism single-nucleotide polymorphism] was discovered in East Asia involving <scene name='95/952696/Residue_267_new/15'>residue 267</scene> being mutated from serine to phenylalanine. This mutation prevented HBV/HDV infection presumably by blocking the binding site in the pore of NTCP. Another mutation, replacing <scene name='95/952696/Leucine_residues/2'>L27, L31, and L35</scene> with tryptophan residues prevents HBV/HDV infection. Further zooming in on <scene name='95/952696/Leucine_residues_zoomed/1'>these residues</scene>, it is probable that this mutation blocks the preS1 binding site of HBV/HDV. [https://en.wikipedia.org/wiki/Myristoylation Myristoylation] of the HBV/HDV capsid is also vital for recognition by NTCP, as well as residues 8-17 on HBV/HDV (sequence: NPLGFFPDHQ)<ref name="Park"/>. Two mechanisms have been proposed for how HBV/HDV binds to NTCP. The first mechanism involves binding of the myristoyl group to the host cell membrane, while residues 8-17 interact with NTCP residues <scene name='95/952696/Residues_157-165_new/1'>157-165</scene>. The second mechanism involves binding of the myristoyl group with residues 157-165 in the pore.<Ref name="Zhang"> Zhang X, Zhang Q, Peng Q, Zhou J, Liao L, Sun X, Zhang L, Gong T. Hepatitis B virus preS1-derived lipopeptide functionalized liposomes for targeting of hepatic cells. Biomaterials. 2014 Jul;35(23):6130-41. [https://dx.doi.org/10.1016/j.biomaterials.2014.04.037 DOI: 10.1016/j.biomaterials.2014.04.037]. </Ref> | ||
== Medical Relevance == | == Medical Relevance == | ||
