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Infectious Diseases Research

Research Overview

A virus enters a target cell by binding to its receptor on the cell surface, initiating a series of conformational changes that result in fusion of the viral and cellular membranes. Membrane fusion provides viral capsid and genome to access the cytoplasm, beginning the next round of replication.
One of the most important insights one can have about a virus derives from its cellular receptor. The Choe laboratory has identified the receptors and related entry cofactors for several clinically important viruses, combining biochemical, cell biological, and structural data. These include CCR5 and other coreceptors for HIV-1, ACE2 as the receptor for SARS-CoV, and TFR1 as the receptor for all New World hemorrhagic fever arenaviruses. In addition to receptor/coreceptor identification, we observed that tyrosine sulfation, a post-translational modification, is the sole common feature of all known HIV-1 coreceptors and essential for their coreceptor function. We also found lysosomal enzymes, cathepsins B and L, are essential for SARS-CoV entry, TIM1 is a general entry enhancing host factor for many viruses, and AXL mediates Zika virus infection of fetal endothelial cells, which could contribute to fetal microcephaly.

Applying our experience with viral entry, we recently developed an AAV vector significantly enhanced in its ability to transduce skeletal muscle, a useful property for intramuscular delivery of vaccines. We are currently developing AAV vectors and other vehicles that specifically target other types of cells including CD4+-T cells or B cells. In collaboration with the Farzan lab, my lab also seeks to improve anti-viral protein therapeutics, using B-cell engineering and a combined strategy of in vitro selection and natural in vivo maturation. In addition, my lab pursues to find strategies to minimize antibody-dependent-enhancement (ADE) of dengue virus infection with the goal of making a useful contribution to dengue vaccine development.

Research Background

Hyeryun Choe received her PhD from Pennsylvania State University in Cellular and Molecular Biology and was trained as a postdoctoral fellow at Beth Israel Hospital in TFR1 receptor-mediated endocytosis and at Dana Farber Cancer Institute in HIV-1. She started her laboratory at Boston Children's Hospital, moved to the Florida Campus of The Scripps Research Institute, and returned to Boston Children's Hospital in 2023.

Publications

  1. Effect of mRNA-LNP components of two globally-marketed COVID-19 vaccines on efficacy and stability. NPJ Vaccines. 2023 Oct 11; 8(1):156. View Abstract
  2. An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants. Nat Commun. 2023 08 25; 14(1):5191. View Abstract
  3. Heavy-chain CDR3-engineered B cells facilitate in vivo evaluation of HIV-1 vaccine candidates. Immunity. 2023 10 10; 56(10):2408-2424.e6. View Abstract
  4. Corrigendum: Bibliometric and visualized analysis of drug resistance in ovarian cancer from 2013 to 2022. Front Oncol. 2023; 13:1228879. View Abstract
  5. Bibliometric and visualized analysis of drug resistance in ovarian cancer from 2013 to 2022. Front Oncol. 2023; 13:1173863. View Abstract
  6. Cytoplasmic Tail Truncation Stabilizes S1-S2 Association and Enhances S Protein Incorporation into SARS-CoV-2 Pseudovirions. J Virol. 2023 03 30; 97(3):e0165022. View Abstract
  7. Clinical Antiviral Drug Arbidol Inhibits Infection by SARS-CoV-2 and Variants through Direct Binding to the Spike Protein. ACS Chem Biol. 2021 12 17; 16(12):2845-2851. View Abstract
  8. Mechanisms of SARS-CoV-2 entry into cells. Nat Rev Mol Cell Biol. 2022 01; 23(1):3-20. View Abstract
  9. An Engineered Receptor-Binding Domain Improves the Immunogenicity of Multivalent SARS-CoV-2 Vaccines. mBio. 2021 05 11; 12(3). View Abstract
  10. How SARS-CoV-2 first adapted in humans. Science. 2021 04 30; 372(6541):466-467. View Abstract
  11. Mutations derived from horseshoe bat ACE2 orthologs enhance ACE2-Fc neutralization of SARS-CoV-2. PLoS Pathog. 2021 04; 17(4):e1009501. View Abstract
  12. Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2. PLoS Pathog. 2021 01; 17(1):e1009212. View Abstract
  13. Phosphatidylethanolamine and Phosphatidylserine Synergize To Enhance GAS6/AXL-Mediated Virus Infection and Efferocytosis. J Virol. 2020 12 22; 95(2). View Abstract
  14. SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity. Nat Commun. 2020 11 26; 11(1):6013. View Abstract
  15. An engineered receptor-binding domain improves the immunogenicity of multivalent SARS-CoV-2 vaccines. bioRxiv. 2020 Nov 18. View Abstract
  16. AAV vectors engineered to target insulin receptor greatly enhance intramuscular gene delivery. Mol Ther Methods Clin Dev. 2020 Dec 11; 19:496-506. View Abstract
  17. Functional importance of the D614G mutation in the SARS-CoV-2 spike protein. Biochem Biophys Res Commun. 2021 01 29; 538:108-115. View Abstract
  18. Transferrin receptor 1 is a cellular receptor for human heme-albumin. Commun Biol. 2020 10 27; 3(1):621. View Abstract
  19. A Single Immunization with Nucleoside-Modified mRNA Vaccines Elicits Strong Cellular and Humoral Immune Responses against SARS-CoV-2 in Mice. Immunity. 2020 10 13; 53(4):724-732.e7. View Abstract
  20. Oregano Oil and Its Principal Component, Carvacrol, Inhibit HIV-1 Fusion into Target Cells. J Virol. 2020 07 16; 94(15). View Abstract
  21. Mutations from bat ACE2 orthologs markedly enhance ACE2-Fc neutralization of SARS-CoV-2. bioRxiv. 2020 Jun 30. View Abstract
  22. The D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivity. bioRxiv. 2020 Jun 12. View Abstract
  23. Zika Virus-Immune Plasmas from Symptomatic and Asymptomatic Individuals Enhance Zika Pathogenesis in Adult and Pregnant Mice. mBio. 2019 07 02; 10(4). View Abstract
  24. Label-Free Pathogen Detection by a Deoxyribozyme Cascade with Visual Signal Readout. Sens Actuators B Chem. 2019 Mar 01; 282:945-951. View Abstract
  25. Potent suppression of HIV-1 cell attachment by Kudzu root extract. Retrovirology. 2018 09 20; 15(1):64. View Abstract
  26. Diverse pathways of escape from all well-characterized VRC01-class broadly neutralizing HIV-1 antibodies. PLoS Pathog. 2018 08; 14(8):e1007238. View Abstract
  27. Ontogeny of the B- and T-cell response in a primary Zika virus infection of a dengue-naïve individual during the 2016 outbreak in Miami, FL. PLoS Negl Trop Dis. 2017 12; 11(12):e0006000. View Abstract
  28. AXL-dependent infection of human fetal endothelial cells distinguishes Zika virus from other pathogenic flaviviruses. Proc Natl Acad Sci U S A. 2017 02 21; 114(8):2024-2029. View Abstract
  29. Zika virus infection during the period of maximal brain growth causes microcephaly and corticospinal neuron apoptosis in wild type mice. Sci Rep. 2016 10 07; 6:34793. View Abstract
  30. Ebselen, a Small-Molecule Capsid Inhibitor of HIV-1 Replication. Antimicrob Agents Chemother. 2016 Apr; 60(4):2195-208. View Abstract
  31. Virion-associated phosphatidylethanolamine promotes TIM1-mediated infection by Ebola, dengue, and West Nile viruses. Proc Natl Acad Sci U S A. 2015 Nov 24; 112(47):14682-7. View Abstract
  32. Novel Arenavirus Entry Inhibitors Discovered by Using a Minigenome Rescue System for High-Throughput Drug Screening. J Virol. 2015 Aug; 89(16):8428-43. View Abstract
  33. Human and host species transferrin receptor 1 use by North American arenaviruses. J Virol. 2014 Aug; 88(16):9418-28. View Abstract
  34. Dual host-virus arms races shape an essential housekeeping protein. PLoS Biol. 2013; 11(5):e1001571. View Abstract
  35. TIM-family proteins promote infection of multiple enveloped viruses through virion-associated phosphatidylserine. PLoS Pathog. 2013 Mar; 9(3):e1003232. View Abstract
  36. Enhanced recognition and neutralization of HIV-1 by antibody-derived CCR5-mimetic peptide variants. J Virol. 2012 Nov; 86(22):12417-21. View Abstract
  37. An antibody recognizing the apical domain of human transferrin receptor 1 efficiently inhibits the entry of all new world hemorrhagic Fever arenaviruses. J Virol. 2012 Apr; 86(7):4024-8. View Abstract
  38. Transferrin receptor 1 in the zoonosis and pathogenesis of New World hemorrhagic fever arenaviruses. Curr Opin Microbiol. 2011 Aug; 14(4):476-82. View Abstract
  39. A tyrosine-sulfated CCR5-mimetic peptide promotes conformational transitions in the HIV-1 envelope glycoprotein. J Virol. 2011 Aug; 85(15):7563-71. View Abstract
  40. Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus. PLoS Pathog. 2011 Jan 06; 7(1):e1001258. View Abstract
  41. Structural basis for receptor recognition by New World hemorrhagic fever arenaviruses. Nat Struct Mol Biol. 2010 Apr; 17(4):438-44. View Abstract
  42. Mutagenesis and evolution of sulfated antibodies using an expanded genetic code. Biochemistry. 2009 Sep 22; 48(37):8891-8. View Abstract
  43. A New World primate deficient in tetherin-mediated restriction of human immunodeficiency virus type 1. J Virol. 2009 Sep; 83(17):8771-80. View Abstract
  44. Host-species transferrin receptor 1 orthologs are cellular receptors for nonpathogenic new world clade B arenaviruses. PLoS Pathog. 2009 Apr; 5(4):e1000358. View Abstract
  45. Chapter 7. Tyrosine sulfation of HIV-1 coreceptors and other chemokine receptors. Methods Enzymol. 2009; 461:147-70. View Abstract
  46. Protein evolution with an expanded genetic code. Proc Natl Acad Sci U S A. 2008 Nov 18; 105(46):17688-93. View Abstract
  47. Influenza A virus neuraminidase limits viral superinfection. J Virol. 2008 May; 82(10):4834-43. View Abstract
  48. Receptor determinants of zoonotic transmission of New World hemorrhagic fever arenaviruses. Proc Natl Acad Sci U S A. 2008 Feb 19; 105(7):2664-9. View Abstract
  49. The S proteins of human coronavirus NL63 and severe acute respiratory syndrome coronavirus bind overlapping regions of ACE2. Virology. 2007 Oct 25; 367(2):367-74. View Abstract
  50. Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses. Nature. 2007 Mar 01; 446(7131):92-6. View Abstract
  51. Severe acute respiratory syndrome coronavirus entry as a target of antiviral therapies. Antivir Ther. 2007; 12(4 Pt B):639-50. View Abstract
  52. Tyrosine sulfate trapped by amber. Nat Biotechnol. 2006 Nov; 24(11):1361-2. View Abstract
  53. A tyrosine-sulfated peptide derived from the heavy-chain CDR3 region of an HIV-1-neutralizing antibody binds gp120 and inhibits HIV-1 infection. J Biol Chem. 2006 Sep 29; 281(39):28529-35. View Abstract
  54. Animal origins of the severe acute respiratory syndrome coronavirus: insight from ACE2-S-protein interactions. J Virol. 2006 May; 80(9):4211-9. View Abstract
  55. Conserved receptor-binding domains of Lake Victoria marburgvirus and Zaire ebolavirus bind a common receptor. J Biol Chem. 2006 Jun 09; 281(23):15951-8. View Abstract
  56. Insights from the association of SARS-CoV S-protein with its receptor, ACE2. Adv Exp Med Biol. 2006; 581:209-18. View Abstract
  57. SARS-CoV, but not HCoV-NL63, utilizes cathepsins to infect cells: viral entry. Adv Exp Med Biol. 2006; 581:335-8. View Abstract
  58. SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells. J Biol Chem. 2006 Feb 10; 281(6):3198-203. View Abstract
  59. T-bet is required for optimal proinflammatory CD4+ T-cell trafficking. Blood. 2005 Nov 15; 106(10):3432-9. View Abstract
  60. Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. EMBO J. 2005 Apr 20; 24(8):1634-43. View Abstract
  61. Sulphated tyrosines mediate association of chemokines and Plasmodium vivax Duffy binding protein with the Duffy antigen/receptor for chemokines (DARC). Mol Microbiol. 2005 Mar; 55(5):1413-22. View Abstract
  62. Mapping binding residues in the Plasmodium vivax domain that binds Duffy antigen during red cell invasion. Mol Microbiol. 2005 Mar; 55(5):1423-34. View Abstract
  63. Angiotensin-converting enzyme 2: a functional receptor for SARS coronavirus. Cell Mol Life Sci. 2004 Nov; 61(21):2738-43. View Abstract
  64. Retroviruses pseudotyped with the severe acute respiratory syndrome coronavirus spike protein efficiently infect cells expressing angiotensin-converting enzyme 2. J Virol. 2004 Oct; 78(19):10628-35. View Abstract
  65. Efficient replication of severe acute respiratory syndrome coronavirus in mouse cells is limited by murine angiotensin-converting enzyme 2. J Virol. 2004 Oct; 78(20):11429-33. View Abstract
  66. N-linked glycosylation in the CXCR4 N-terminus inhibits binding to HIV-1 envelope glycoproteins. Virology. 2004 Jun 20; 324(1):140-50. View Abstract
  67. Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association. Proc Natl Acad Sci U S A. 2004 Feb 24; 101(8):2536-41. View Abstract
  68. Structural basis of tyrosine sulfation and VH-gene usage in antibodies that recognize the HIV type 1 coreceptor-binding site on gp120. Proc Natl Acad Sci U S A. 2004 Mar 02; 101(9):2706-11. View Abstract
  69. A 193-amino acid fragment of the SARS coronavirus S protein efficiently binds angiotensin-converting enzyme 2. J Biol Chem. 2004 Jan 30; 279(5):3197-201. View Abstract
  70. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003 Nov 27; 426(6965):450-4. View Abstract
  71. C5L2, a nonsignaling C5A binding protein. Biochemistry. 2003 Aug 12; 42(31):9406-15. View Abstract
  72. Tyrosine sulfation of human antibodies contributes to recognition of the CCR5 binding region of HIV-1 gp120. Cell. 2003 Jul 25; 114(2):161-70. View Abstract
  73. Sulfation of tyrosine 174 in the human C3a receptor is essential for binding of C3a anaphylatoxin. J Biol Chem. 2003 Sep 26; 278(39):37902-8. View Abstract
  74. Tyrosine-sulfated peptides functionally reconstitute a CCR5 variant lacking a critical amino-terminal region. J Biol Chem. 2002 Oct 25; 277(43):40397-402. View Abstract
  75. The role of post-translational modifications of the CXCR4 amino terminus in stromal-derived factor 1 alpha association and HIV-1 entry. J Biol Chem. 2002 Aug 16; 277(33):29484-9. View Abstract
  76. Sialylated O-glycans and sulfated tyrosines in the NH2-terminal domain of CC chemokine receptor 5 contribute to high affinity binding of chemokines. J Exp Med. 2001 Dec 03; 194(11):1661-73. View Abstract
  77. Sulfated tyrosines contribute to the formation of the C5a docking site of the human C5a anaphylatoxin receptor. J Exp Med. 2001 May 07; 193(9):1059-66. View Abstract
  78. Apelin, the natural ligand of the orphan seven-transmembrane receptor APJ, inhibits human immunodeficiency virus type 1 entry. J Virol. 2000 Dec; 74(24):11972-6. View Abstract
  79. A tyrosine-sulfated peptide based on the N terminus of CCR5 interacts with a CD4-enhanced epitope of the HIV-1 gp120 envelope glycoprotein and inhibits HIV-1 entry. J Biol Chem. 2000 Oct 27; 275(43):33516-21. View Abstract
  80. BACE2, a beta -secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein. Proc Natl Acad Sci U S A. 2000 Aug 15; 97(17):9712-7. View Abstract
  81. Adaptation of a CCR5-using, primary human immunodeficiency virus type 1 isolate for CD4-independent replication. J Virol. 1999 Oct; 73(10):8120-6. View Abstract
  82. Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry. Cell. 1999 Mar 05; 96(5):667-76. View Abstract
  83. Stabilization of human immunodeficiency virus type 1 envelope glycoprotein trimers by disulfide bonds introduced into the gp41 glycoprotein ectodomain. J Virol. 1998 Sep; 72(9):7620-5. View Abstract
  84. The orphan seven-transmembrane receptor apj supports the entry of primary T-cell-line-tropic and dualtropic human immunodeficiency virus type 1. J Virol. 1998 Jul; 72(7):6113-8. View Abstract
  85. Structural interactions between chemokine receptors, gp120 Env and CD4. Semin Immunol. 1998 Jun; 10(3):249-57. View Abstract
  86. The bis-azo compound FP-21399 inhibits HIV-1 replication by preventing viral entry. Virology. 1998 May 10; 244(2):530-41. View Abstract
  87. A tyrosine-rich region in the N terminus of CCR5 is important for human immunodeficiency virus type 1 entry and mediates an association between gp120 and CCR5. J Virol. 1998 Feb; 72(2):1160-4. View Abstract
  88. Use of murine CXCR-4 as a second receptor by some T-cell-tropic human immunodeficiency viruses. J Virol. 1998 Feb; 72(2):1652-6. View Abstract
  89. CD4-independent binding of SIV gp120 to rhesus CCR5. Science. 1997 Nov 21; 278(5342):1470-3. View Abstract
  90. Two orphan seven-transmembrane segment receptors which are expressed in CD4-positive cells support simian immunodeficiency virus infection. J Exp Med. 1997 Aug 04; 186(3):405-11. View Abstract
  91. CCR5 levels and expression pattern correlate with infectability by macrophage-tropic HIV-1, in vitro. J Exp Med. 1997 May 05; 185(9):1681-91. View Abstract
  92. HIV-1 entry and macrophage inflammatory protein-1beta-mediated signaling are independent functions of the chemokine receptor CCR5. J Biol Chem. 1997 Mar 14; 272(11):6854-7. View Abstract
  93. Utilization of C-C chemokine receptor 5 by the envelope glycoproteins of a pathogenic simian immunodeficiency virus, SIVmac239. J Virol. 1997 Mar; 71(3):2522-7. View Abstract
  94. CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia. Nature. 1997 Feb 13; 385(6617):645-9. View Abstract
  95. CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5. Nature. 1996 Nov 14; 384(6605):179-83. View Abstract
  96. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature. 1996 Aug 29; 382(6594):829-33. View Abstract
  97. The beta-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell. 1996 Jun 28; 85(7):1135-48. View Abstract
  98. Adaptation of human immunodeficiency virus type 1 to cells expressing a binding-deficient CD4 mutant (lysine 46 to aspartic acid). J Virol. 1995 May; 69(5):2801-10. View Abstract
  99. Contribution of charged amino acids in the CDR2 region of CD4 to HIV-1 gp120 binding. J Acquir Immune Defic Syndr (1988). 1992; 5(2):204-10. View Abstract
  100. Rabbit reticulocyte coated vesicles carrying the transferrin-transferrin receptor complex: I. Purification and partial characterization. Blood. 1987 Oct; 70(4):1035-9. View Abstract

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