Sandbox Reserved 1793: Difference between revisions

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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"/> This S267F mutation is a [https://en.wikipedia.org/wiki/Single-nucleotide_polymorphism single-nucleotide polymorphism], where a change in one nucleotide in the sequence has caused a lack of bile salt transport activity or viral infection. <Ref name = "Park"/> It is hypothesized that due to the lack of bile salt transport in this mutation that some aspect or state of bile salt transport is necessary for HBV and HDV infection, meaning the two functionally overlap. <Ref name = "Park"/>
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"/> This S267F mutation is a [https://en.wikipedia.org/wiki/Single-nucleotide_polymorphism single-nucleotide polymorphism], where a change in one nucleotide in the sequence has caused a lack of bile salt transport activity or viral infection. <Ref name = "Park"/> It is hypothesized that due to the lack of bile salt transport in this mutation that some aspect or state of bile salt transport is necessary for HBV and HDV infection, meaning the two functionally overlap. <Ref name = "Park"/>


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, as cells overexpressing NTCP alone had low infection efficiency. <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, as cells overexpressing NTCP alone had low infection efficiency. <Ref name = "Herrscher"/>  




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