1932

Abstract

My grandparents were immigrants. My paternal grandfather was illiterate. Yet my parents were able to complete college and to become teachers. I had a conventional upbringing in a small town in Florida, graduating from high school in 1960. I was fortunate enough to graduate cum laude from Florida State University and to earn other credentials leading to faculty positions at outstanding institutions of higher education: the University of Chicago and Northwestern University. At a time when women were rarely the leaders of research groups, I was able to establish a well-funded research program and to make contributions to our understanding of viral entry into cells. My best research was done after I became confident enough to seek productive interactions with collaborators. I am grateful for the collaborators and collaborations that moved our field forward and for my trainees who have gone on to successes in many different careers.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-virology-100520-012840
2022-09-29
2025-04-19
Loading full text...

Full text loading...

/deliver/fulltext/virology/9/1/annurev-virology-100520-012840.html?itemId=/content/journals/10.1146/annurev-virology-100520-012840&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Spear PG, Roizman B. 1967.. Buoyant density of herpes simplex virus in solutions of caesium chloride. . Nature 214::71314
    [Google Scholar]
  2. 2.
    Roizman B, Spear PG. 1968.. Preparation of herpes simplex virus of high titer. . J. Virol. 2::8384
    [Google Scholar]
  3. 3.
    Spear PG, Roizman B. 1968.. The proteins specified by herpes simplex virus. I. Time of synthesis, transfer into nuclei, and properties of proteins made in productively infected cells. . Virology 36::54555
    [Google Scholar]
  4. 4.
    Spear PG, Roizman B. 1968.. An improved procedure for H3 and C14 counting in acrylamide gels with a nonaqueous scintillation system. . Anal. Biochem. 26::197200
    [Google Scholar]
  5. 5.
    Spear PG, Roizman B. 1972.. Proteins specified by herpes simplex virus. V. Purification and structural proteins of the herpesvirion. . J. Virol. 9::14359
    [Google Scholar]
  6. 6.
    Spear PG, Keller JM, Roizman B. 1970.. Proteins specified by herpes simplex virus. II. Viral glycoproteins associated with cellular membranes. . J. Virol. 5::12331
    [Google Scholar]
  7. 7.
    Spear PG, Roizman B. 1970.. Proteins specified by herpes simplex virus, IV. Site of glycosylation and accumulation of viral membrane proteins. . PNAS 66::73037
    [Google Scholar]
  8. 8.
    Roizman B, Spear PG. 1971.. Herpesvirus antigens on cell membranes detected by centrifugation of membrane-antibody complexes. . Science 171::298300
    [Google Scholar]
  9. 9.
    Heine JW, Spear PG, Roizman B. 1972.. Proteins specified by herpes simplex virus. VI. Viral proteins in the plasma membrane. . J. Virol. 9::43139
    [Google Scholar]
  10. 10.
    Loret S, Guay G, Lippe R. 2008.. Comprehensive characterization of extracellular herpes simplex virus type 1 virions. . J. Virol. 82::860518
    [Google Scholar]
  11. 11.
    Spear PG, Wang AL, Rutishauser U, Edelman GM. 1973.. Characterization of splenic lymphoid cells in fetal and newborn mice. . J. Exp. Med. 138::55773
    [Google Scholar]
  12. 12.
    Spear PG, Edelman GM. 1974.. Maturation of the humoral immune response in mice. . J. Exp. Med. 139::24963
    [Google Scholar]
  13. 13.
    Spear PG. 1976.. Membrane proteins specified by herpes simplex viruses. I. Identification of four glycoprotein precursors and their products in type 1-infected cells. . J. Virol. 17::9911008
    [Google Scholar]
  14. 14.
    Spear PG. 1993.. Entry of alphaherpesviruses into cells. . Semin. Virol. 4::16780
    [Google Scholar]
  15. 15.
    Hilterbrand AT, Daly RE, Heldwein EE. 2021.. Contributions of the four essential entry glycoproteins to HSV-1 tropism and the selection of entry routes. . mBio 12::e0014321
    [Google Scholar]
  16. 16.
    Hilterbrand AT, Heldwein EE. 2019.. Go go gadget glycoprotein!: HSV-1 draws on its sizeable glycoprotein tool kit to customize its diverse entry routes. . PLOS Pathog. 15::e1007660
    [Google Scholar]
  17. 17.
    Shukla D, Spear PG. 2001.. Herpesviruses and heparan sulfate: an intimate relationship in aid of viral entry. . J. Clin. Invest. 108::50310
    [Google Scholar]
  18. 18.
    Parry C, Bell S, Minson T, Browne H. 2005.. Herpes simplex virus type 1 glycoprotein H binds to αvβ3 integrins. . J. Gen. Virol. 86::710
    [Google Scholar]
  19. 19.
    Galdiero M, Whiteley A, Bruun B, Bell S, Minson T, Browne H. 1997.. Site-directed and linker insertion mutagenesis of herpes simplex virus type 1 glycoprotein H. . J. Virol. 71::216370
    [Google Scholar]
  20. 20.
    Satoh T, Arii J, Suenaga T, Wang J, Kogure A, et al. 2008.. PILRα is a herpes simplex virus-1 entry coreceptor that associates with glycoprotein B. . Cell 132::93544
    [Google Scholar]
  21. 21.
    Spear PG, Eisenberg RJ, Cohen GH. 2000.. Three classes of cell surface receptors for alphaherpesvirus entry. . Virology 275::18
    [Google Scholar]
  22. 22.
    Eisenberg RJ, Atanasiu D, Cairns TM, Gallagher JR, Krummenacher C, Cohen GH. 2012.. Herpes virus fusion and entry: a story with many characters. . Viruses 4::80032
    [Google Scholar]
  23. 23.
    Vollmer B, Prazak V, Vasishtan D, Jefferys EE, Hernandez-Duran A, et al. 2020.. The prefusion structure of herpes simplex virus glycoprotein B. . Sci. Adv. 6::eabc1726
    [Google Scholar]
  24. 24.
    Heldwein EE, Lou H, Bender FC, Cohen GH, Eisenberg RJ, Harrison SC. 2006.. Crystal structure of glycoprotein B from herpes simplex virus 1. . Science 313::21720
    [Google Scholar]
  25. 25.
    Johnson DC, Spear PG. 1983.. O-linked oligosaccharides are acquired by herpes simplex virus glycoproteins in the Golgi apparatus. . Cell 32::98797
    [Google Scholar]
  26. 26.
    Nahmias AJ, Kibrick S. 1964.. Inhibitory effect of heparin on herpes simplex virus. . J. Bacteriol. 87::106066
    [Google Scholar]
  27. 27.
    WuDunn D, Spear PG. 1989.. Initial interaction of herpes simplex virus with cells is binding to heparan sulfate. . J. Virol. 63::5258
    [Google Scholar]
  28. 28.
    Shieh MT, WuDunn D, Montgomery RI, Esko JD, Spear PG. 1992.. Cell surface receptors for herpes simplex virus are heparan sulfate proteoglycans. . J. Cell Biol. 116::127381
    [Google Scholar]
  29. 29.
    Herold BC, WuDunn D, Soltys N, Spear PG. 1991.. Glycoprotein C of herpes simplex virus type 1 plays a principal role in the adsorption of virus to cells and in infectivity. . J. Virol. 65::109098
    [Google Scholar]
  30. 30.
    Herold BC, Visalli RJ, Susmarski N, Brandt CR, Spear PG. 1994.. Glycoprotein C-independent binding of herpes simplex virus to cells requires cell surface heparan sulphate and glycoprotein B. . J. Gen. Virol. 75:(Part 6):121122
    [Google Scholar]
  31. 31.
    Manservigi R, Spear PG, Buchan A. 1977.. Cell fusion induced by herpes simplex virus is promoted and suppressed by different viral glycoproteins. . PNAS 74::391317
    [Google Scholar]
  32. 32.
    Gruenheid S, Gatzke L, Meadows H, Tufaro F. 1993.. Herpes simplex virus infection and propagation in a mouse L cell mutant lacking heparan sulfate proteoglycans. . J. Virol. 67::93100
    [Google Scholar]
  33. 33.
    Pertel PE, Spear PG. 1996.. Modified entry and syncytium formation by herpes simplex virus type 1 mutants selected for resistance to heparin inhibition. . Virology 226::2233
    [Google Scholar]
  34. 34.
    Clausen TM, Sandoval DR, Spliid CB, Pihl J, Perrett HR, et al. 2020.. SARS-CoV-2 infection depends on cellular heparan sulfate and ACE2. . Cell 183::104357.e15
    [Google Scholar]
  35. 35.
    Shieh MT, Spear PG. 1994.. Herpesvirus-induced cell fusion that is dependent on cell surface heparan sulfate or soluble heparin. . J. Virol. 68::122428
    [Google Scholar]
  36. 36.
    Haffey ML, Spear PG. 1980.. Alterations in glycoprotein gB specified by mutants and their partial revertants in herpes simplex virus type 1 and relationship to other mutant phenotypes. . J. Virol. 35::11428
    [Google Scholar]
  37. 37.
    Sarmiento M, Haffey M, Spear PG. 1979.. Membrane proteins specified by herpes simplex viruses. III. Role of glycoprotein VP7(B2) in virion infectivity. . J. Virol. 29::114958
    [Google Scholar]
  38. 38.
    Cai WH, Gu B, Person S. 1988.. Role of glycoprotein B of herpes simplex virus type 1 in viral entry and cell fusion. . J. Virol. 62::2596604
    [Google Scholar]
  39. 39.
    Claesson-Welsh L, Spear PG. 1986.. Oligomerization of herpes simplex virus glycoprotein B. . J. Virol. 60::8036
    [Google Scholar]
  40. 40.
    Sarmiento M, Spear PG. 1979.. Membrane proteins specified by herpes simplex viruses. IV. Conformation of the virion glycoprotein designated VP7(B2). . J. Virol. 29::115967
    [Google Scholar]
  41. 41.
    Para MF, Parish ML, Noble AG, Spear PG. 1985.. Potent neutralizing activity associated with anti-glycoprotein D specificity among monoclonal antibodies selected for binding to herpes simplex virions. . J. Virol. 55::48388
    [Google Scholar]
  42. 42.
    Stannard LM, Fuller AO, Spear PG. 1987.. Herpes simplex virus glycoproteins associated with different morphological entities projecting from the virion envelope. . J. Gen. Virol. 68::71525
    [Google Scholar]
  43. 43.
    Campadelli-Fiume G, Arsenakis M, Farabegoli F, Roizman B. 1988.. Entry of herpes simplex virus 1 in BJ cells that constitutively express viral glycoprotein D is by endocytosis and results in degradation of the virus. . J. Virol. 62::15967
    [Google Scholar]
  44. 44.
    Johnson RM, Spear PG. 1989.. Herpes simplex virus glycoprotein D mediates interference with herpes simplex virus infection. . J. Virol. 63::81927
    [Google Scholar]
  45. 45.
    Vogt PK. 1970.. Envelope classification of avian RNA tumor viruses. . Bibl. Haematol. 36::15367
    [Google Scholar]
  46. 46.
    Ligas MW, Johnson DC. 1988.. A herpes simplex virus mutant in which glycoprotein D sequences are replaced by β-galactosidase sequences binds to but is unable to penetrate into cells. . J. Virol. 62::148694
    [Google Scholar]
  47. 47.
    Johnson DC, Ligas MW. 1988.. Herpes simplex viruses lacking glycoprotein D are unable to inhibit virus penetration: quantitative evidence for virus-specific cell surface receptors. . J. Virol. 62::460512
    [Google Scholar]
  48. 48.
    Fuller AO, Spear PG. 1985.. Specificities of monoclonal and polyclonal antibodies that inhibit adsorption of herpes simplex virus to cells and lack of inhibition by potent neutralizing antibodies. . J. Virol. 55::47582
    [Google Scholar]
  49. 49.
    Fuller AO, Spear PG. 1987.. Anti-glycoprotein D antibodies that permit adsorption but block infection by herpes simplex virus 1 prevent virion-cell fusion at the cell surface. . PNAS 84::545458
    [Google Scholar]
  50. 50.
    Noble AG, Lee GT, Sprague R, Parish ML, Spear PG. 1983.. Anti-gD monoclonal antibodies inhibit cell fusion induced by herpes simplex virus type 1. . Virology 129::21824
    [Google Scholar]
  51. 51.
    Dean HJ, Terhune SS, Shieh MT, Susmarski N, Spear PG. 1994.. Single amino acid substitutions in gD of herpes simplex virus 1 confer resistance to gD-mediated interference and cause cell-type-dependent alterations in infectivity. . Virology 199::6780
    [Google Scholar]
  52. 52.
    Fuller AO, Santos RE, Spear PG. 1989.. Neutralizing antibodies specific for glycoprotein H of herpes simplex virus permit viral attachment to cells but prevent penetration. . J. Virol. 63::343543
    [Google Scholar]
  53. 53.
    Desai PJ, Schaffer PA, Minson AC. 1988.. Excretion of non-infectious virus particles lacking glycoprotein H by a temperature-sensitive mutant of herpes simplex virus type 1: evidence that gH is essential for virion infectivity. . J. Gen. Virol. 69:(Part 6):114756
    [Google Scholar]
  54. 54.
    Montgomery RI, Warner MS, Lum BJ, Spear PG. 1996.. Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF/NGF receptor family. . Cell 87::42736
    [Google Scholar]
  55. 55.
    Sedy J, Bekiaris V, Ware CF. 2014.. Tumor necrosis factor superfamily in innate immunity and inflammation. . Cold Spring Harb. Perspect. Biol. 7::a016279
    [Google Scholar]
  56. 56.
    Burn Aschner C, Loh LN, Galen B, Delwel I, Jangra RK, et al. 2020.. HVEM signaling promotes protective antibody-dependent cellular cytotoxicity (ADCC) vaccine responses to herpes simplex viruses. . Sci. Immunol. 5::eaax2454
    [Google Scholar]
  57. 57.
    Warner MS, Geraghty RJ, Martinez WM, Montgomery RI, Whitbeck JC, et al. 1998.. A cell surface protein with herpesvirus entry activity (HveB) confers susceptibility to infection by mutants of herpes simplex virus type 1, herpes simplex virus type 2, and pseudorabies virus. . Virology 246::17989
    [Google Scholar]
  58. 58.
    Freistadt MS, Kaplan G, Racaniello VR. 1990.. Heterogeneous expression of poliovirus receptor-related proteins in human cells and tissues. . Mol. Cell. Biol. 10::57006
    [Google Scholar]
  59. 59.
    Takahashi K, Nakanishi H, Miyahara M, Mandai K, Satoh K, et al. 1999.. Nectin/PRR: an immunoglobulin-like cell adhesion molecule recruited to cadherin-based adherens junctions through interaction with Afadin, a PDZ domain-containing protein. . J. Cell Biol. 145::53949
    [Google Scholar]
  60. 60.
    Geraghty RJ, Krummenacher C, Cohen GH, Eisenberg RJ, Spear PG. 1998.. Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and poliovirus receptor. . Science 280::161820
    [Google Scholar]
  61. 61.
    Mizutani K, Miyata M, Shiotani H, Kameyama T, Takai Y. 2021.. Nectins and nectin-like molecules in synapse formation and involvement in neurological diseases. . Mol. Cell. Neurosci. 115::103653
    [Google Scholar]
  62. 62.
    Yoon M, Spear PG. 2002.. Disruption of adherens junctions liberates nectin-1 to serve as receptor for herpes simplex virus and pseudorabies virus entry. . J. Virol. 76::72038
    [Google Scholar]
  63. 63.
    Whitbeck JC, Peng C, Lou H, Xu R, Willis SH, et al. 1997.. Glycoprotein D of herpes simplex virus (HSV) binds directly to HVEM, a member of the tumor necrosis factor receptor superfamily and a mediator of HSV entry. . J. Virol. 71::608393
    [Google Scholar]
  64. 64.
    Krummenacher C, Nicola AV, Whitbeck JC, Lou H, Hou W, et al. 1998.. Herpes simplex virus glycoprotein D can bind to poliovirus receptor-related protein 1 or herpesvirus entry mediator, two structurally unrelated mediators of virus entry. . J. Virol. 72::706474
    [Google Scholar]
  65. 65.
    Nicola AV, Ponce de Leon M, Xu R, Hou W, Whitbeck JC, et al. 1998.. Monoclonal antibodies to distinct sites on herpes simplex virus (HSV) glycoprotein D block HSV binding to HVEM. . J. Virol. 72::3595601
    [Google Scholar]
  66. 66.
    Krummenacher C, Rux AH, Whitbeck JC, Ponce-de-Leon M, Lou H, et al. 1999.. The first immunoglobulin-like domain of HveC is sufficient to bind herpes simplex virus gD with full affinity, while the third domain is involved in oligomerization of HveC. . J. Virol. 73::812737
    [Google Scholar]
  67. 67.
    Krummenacher C, Supekar VM, Whitbeck JC, Lazear E, Connolly SA, et al. 2005.. Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry. . EMBO J. 24::414453
    [Google Scholar]
  68. 68.
    Carfi A, Willis SH, Whitbeck JC, Krummenacher C, Cohen GH, et al. 2001.. Herpes simplex virus glycoprotein D bound to the human receptor HveA. . Mol. Cell 8::16979
    [Google Scholar]
  69. 69.
    Di Giovine P, Settembre EC, Bhargava AK, Luftig MA, Lou H, et al. 2011.. Structure of herpes simplex virus glycoprotein D bound to the human receptor nectin-1. . PLOS Pathog. 7::e1002277
    [Google Scholar]
  70. 70.
    Yoon M, Spear PG. 2004.. Random mutagenesis of the gene encoding a viral ligand for multiple cell entry receptors to obtain viral mutants altered for receptor usage. . PNAS 101::1725257
    [Google Scholar]
  71. 71.
    Yoon M, Zago A, Shukla D, Spear PG. 2003.. Mutations in the N termini of herpes simplex virus type 1 and 2 gDs alter functional interactions with the entry/fusion receptors HVEM, nectin-2, and 3-O-sulfated heparan sulfate but not with nectin-1. . J. Virol. 77::922131
    [Google Scholar]
  72. 72.
    Manoj S, Jogger CR, Myscofski D, Yoon M, Spear PG. 2004.. Mutations in herpes simplex virus glycoprotein D that prevent cell entry via nectins and alter cell tropism. . PNAS 101::1241421
    [Google Scholar]
  73. 73.
    Jogger CR, Montgomery RI, Spear PG. 2004.. Effects of linker-insertion mutations in herpes simplex virus 1 gD on glycoprotein-induced fusion with cells expressing HVEM or nectin-1. . Virology 318::31826
    [Google Scholar]
  74. 74.
    Geraghty RJ, Jogger CR, Spear PG. 2000.. Cellular expression of alphaherpesvirus gD interferes with entry of homologous and heterologous alphaherpesviruses by blocking access to a shared gD receptor. . Virology 268::14758
    [Google Scholar]
  75. 75.
    Terry-Allison T, Montgomery RI, Warner MS, Geraghty RJ, Spear PG. 2001.. Contributions of gD receptors and glycosaminoglycan sulfation to cell fusion mediated by herpes simplex virus 1. . Virus Res. 74::3945
    [Google Scholar]
  76. 76.
    Pertel PE, Fridberg A, Parish ML, Spear PG. 2001.. Cell fusion induced by herpes simplex virus glycoproteins gB, gD, and gH-gL requires a gD receptor but not necessarily heparan sulfate. . Virology 279::31324
    [Google Scholar]
  77. 77.
    Fan Q, Lin E, Satoh T, Arase H, Spear PG. 2009.. Differential effects on cell fusion activity of mutations in herpes simplex virus 1 glycoprotein B (gB) dependent on whether a gD receptor or a gB receptor is overexpressed. . J. Virol. 83::738490
    [Google Scholar]
  78. 78.
    Shukla D, Dal Canto MC, Rowe CL, Spear PG. 2000.. Striking similarity of murine nectin-1α to human nectin-1α (HveC) in sequence and activity as a glycoprotein D receptor for alphaherpesvirus entry. . J. Virol. 74::1177381
    [Google Scholar]
  79. 79.
    Shukla D, Rowe CL, Dong Y, Racaniello VR, Spear PG. 1999.. The murine homolog (Mph) of human herpesvirus entry protein B (HveB) mediates entry of pseudorabies virus but not herpes simplex virus types 1 and 2. . J. Virol. 73::449397
    [Google Scholar]
  80. 80.
    Shukla D, Liu J, Blaiklock P, Shworak NW, Bai X, et al. 1999.. A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry. . Cell 99::1322
    [Google Scholar]
  81. 81.
    Wang Y, Subudhi SK, Anders RA, Lo J, Sun Y, et al. 2005.. The role of herpesvirus entry mediator as a negative regulator of T cell-mediated responses. . J. Clin. Invest. 115::71117
    [Google Scholar]
  82. 82.
    Inagaki M, Irie K, Ishizaki H, Tanaka-Okamoto M, Morimoto K, et al. 2005.. Roles of cell-adhesion molecules nectin 1 and nectin 3 in ciliary body development. . Development 132::152537
    [Google Scholar]
  83. 83.
    Parr MB, Kepple L, McDermott MR, Drew MD, Bozzola JJ, Parr EL. 1994.. A mouse model for studies of mucosal immunity to vaginal infection by herpes simplex virus type 2. . Lab. Invest. 70::36980
    [Google Scholar]
  84. 84.
    Taylor JM, Lin E, Susmarski N, Yoon M, Zago A, et al. 2007.. Alternative entry receptors for herpes simplex virus and their roles in disease. . Cell Host Microbe 2::1928
    [Google Scholar]
  85. 85.
    Kopp SJ, Banisadr G, Glajch K, Maurer UE, Grunewald K, et al. 2009.. Infection of neurons and encephalitis after intracranial inoculation of herpes simplex virus requires the entry receptor nectin-1. . PNAS 106::1791620
    [Google Scholar]
  86. 86.
    Karaba AH, Kopp SJ, Longnecker R. 2011.. Herpesvirus entry mediator and nectin-1 mediate herpes simplex virus 1 infection of the murine cornea. . J. Virol. 85::1004147
    [Google Scholar]
  87. 87.
    Karaba AH, Kopp SJ, Longnecker R. 2012.. Herpesvirus entry mediator is a serotype specific determinant of pathogenesis in ocular herpes. . PNAS 109::2064954
    [Google Scholar]
  88. 88.
    Edwards RG, Kopp SJ, Karaba AH, Wilcox DR, Longnecker R. 2015.. Herpesvirus entry mediator on radiation-resistant cell lineages promotes ocular herpes simplex virus 1 pathogenesis in an entry-independent manner. . mBio 6::e0153215
    [Google Scholar]
/content/journals/10.1146/annurev-virology-100520-012840
Loading
/content/journals/10.1146/annurev-virology-100520-012840
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error