Sandbox Reserved 1793: Difference between revisions
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== HBV Binding and Infection== | == HBV Binding and Infection== | ||
NTCP is the only [https://rupress.org/jcb/article/195/7/1071/54877/The-cell-biology-of-receptor-mediated-virus entry receptor] <Ref name = "Grove"> Grove, J.; Marsh, M. The Cell Biology of Receptor-Mediated Virus Entry. Journal of Cell Biology 2011, 195 (7), 1071–1082. </ref> into the liver for HBV and HDV. <Ref name = "Asami"/> The [https://en.wikipedia.org/wiki/Myristoylation myristolated] PreS1 domain of HBV binds to NTCP through | NTCP is the only [https://rupress.org/jcb/article/195/7/1071/54877/The-cell-biology-of-receptor-mediated-virus entry receptor] <Ref name = "Grove"> Grove, J.; Marsh, M. The Cell Biology of Receptor-Mediated Virus Entry. Journal of Cell Biology 2011, 195 (7), 1071–1082. </ref> into the liver for HBV and HDV. <Ref name = "Asami"/>These viruses are known to use <scene name='95/952721/Hep_patches/2'>two different patches</scene> <font color='#00e080'><b>(residues 84-87 and 157-165)</b></font> on NTCP for binding and entry. The [https://en.wikipedia.org/wiki/Myristoylation myristolated] PreS1 domain of HBV binds to NTCP through the <scene name='95/952721/Hbv_patch_1/1'>first hydrophobic patch</scene> on NTCP containing <font color='#00e080'><b>residues 157-165</b></font> on the open pore surface. <Ref name = "Asami"/> These residues form part of the bile salt transport tunnel resulting in HBV binding and bile salt transport directly competing and interfering with one another. <Ref name = "Asami"/> The <scene name='95/952721/Hbv_patch_2/1'>other hydrophobic patch</scene> consisting of <font color='#00e080'><b>residues 84-87</b></font> found on the N-terminus of NTCP does not overlap with bile salt binding and may be used for the development of [https://en.wikipedia.org/wiki/Antiviral_drug antivirals] that do not inhibit bile uptake <Ref name = "Park"/>. Other minor variations within NTCP provide species specificity for HBV or virus resistance, such as mutant S267F found in East Asia. <Ref name = "Park"/> [EXPLAIN HOW GIVES RESISTANCE] | ||
The exact mechanism by which NTCP mediates viral internalization is still being determined; however, current evidence suggests it works through [https://en.wikipedia.org/wiki/Viral_entry#Entry_via_endocytosis endocytosis.] <Ref name = "Herrscher"> Herrscher C, Roingeard P, Blanchard E. Hepatitis B Virus Entry into Cells. Cells. 2020 Jun 18;9(6):1486. doi: 10.3390/cells9061486. PMID: 32570893; PMCID: PMC7349259. </ref> Once HBV is bound, the NTCP/HBV complex is taken into the cell where viral contents are dumped into the cytoplasm to then begin [https://en.wikipedia.org/wiki/Viral_replication viral replication]. HBV may also interact with other receptors or host cell factors, but NTCP alone is not sufficient for infection. <Ref name = "Herrscher"/> | The exact mechanism by which NTCP mediates viral internalization is still being determined; however, current evidence suggests it works through [https://en.wikipedia.org/wiki/Viral_entry#Entry_via_endocytosis endocytosis.] <Ref name = "Herrscher"> Herrscher C, Roingeard P, Blanchard E. Hepatitis B Virus Entry into Cells. Cells. 2020 Jun 18;9(6):1486. doi: 10.3390/cells9061486. PMID: 32570893; PMCID: PMC7349259. </ref> Once HBV is bound, the NTCP/HBV complex is taken into the cell where viral contents are dumped into the cytoplasm to then begin [https://en.wikipedia.org/wiki/Viral_replication viral replication]. HBV may also interact with other receptors or host cell factors, but NTCP alone is not sufficient for infection. <Ref name = "Herrscher"/> | ||
