Sandbox Reserved 1769: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 32: | Line 32: | ||
=== Mechanism of HBV/HDV Infection === | === Mechanism of HBV/HDV Infection === | ||
HBV and HDV viruses are transported through NTCP via secondary active transport. After binding to NTCP in the <scene name='95/952697/Ntcp_open-pore_state/8'>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. | HBV and HDV viruses are transported through NTCP via secondary active transport. After binding to NTCP in the <scene name='95/952697/Ntcp_open-pore_state/8'>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, although <scene name='95/952696/Residues_84-87_and_157-165_new/1'>two critical sites</scene> | The exact mechanism of how HBV and HDV bind to NTCP is not certain, although Park et. al has identified <scene name='95/952696/Residues_84-87_and_157-165_new/1'>two critical sites</scene> on NTCP: 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_267/3'>Residue 267</scene> being mutated from serine to phenylalanine. This mutation prevented HBV/HDV infection. Another mutation, replacing <scene name='95/952696/Leucine_residues/2'>L27, L31, and L35</scene> with tryptophan presumably blocks the preS1 binding site preventing proper HBV/HDV infection. It has also been shown that [https://en.wikipedia.org/wiki/Myristoylation myristoylation] of the HBV/HDV capsid is vital for recognition by NTCP, as well as residues 8-17 on HBV/HDV (sequence: NPLGFFPDHQ)<ref name="Park" />. There are two proposed mechanisms for how HBV/HDV binds to NTCP. The first proposes binding of the myristoyl group to the host cell membrane, while residues 8-17 interact with NTCP residues 157-165. The second proposes 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 == | ||
