Abstract
The entry process of herpesviruses into host cells is complex and highly variable. It involves a sequence of well-orchestrated events that begin with virus attachment to glycan-containing proteinaceous structures on the cell surface. This initial contact tethers virus particles to the cell surface and results in a cascade of molecular interactions, including the tight interaction of viral envelope glycoproteins to specific cell receptors. These interactions trigger intracellular signaling and finally virus penetration after fusion of the viral envelope with cellular membranes. Based on the engaged cellular receptors and co-receptors, and the subsequent signaling cascades, the entry pathway will be decided on the spot. A number of viral glycoproteins and many cellular receptors and molecules have been identified as players in one or several of these events during virus entry. This chapter will review viral glycoproteins, cellular receptors and signaling cascades associated with the very first interactions of herpesviruses with their target cells.
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References
Abdelgawad A, Azab W, Damiani AM, Baumgartner K, Will H, Osterrieder N, Greenwood AD (2014) Zebra-borne equine herpesvirus type 1 (EHV-1) infection in non-African captive mammals. Vet Microbiol 169(1–2):102–106. doi:10.1016/j.vetmic.2013.12.011
Akhtar J, Shukla D (2009) Viral entry mechanisms: cellular and viral mediators of herpes simplex virus entry. FEBS J 276(24):7228–7236. doi:10.1111/j.1742-4658.2009.07402.x
Alves Dummer L, Pereira Leivas Leite F, van Drunen Littel-van den Hurk S (2014) Bovine herpesvirus glycoprotein D: a review of its structural characteristics and applications in vaccinology. Vet Res 45:111. doi:10.1186/s13567-014-0111-x
Antoine TE, Jones KS, Dale RM, Shukla D, Tiwari V (2014) Zebrafish: modeling for herpes simplex virus infections. Zebrafish 11(1):17–25. doi:10.1089/zeb.2013.0920
Arii J, Uema M, Morimoto T, Sagara H, Akashi H, Ono E, Arase H, Kawaguchi Y (2009) Entry of herpes simplex virus 1 and other alphaherpesviruses via the paired immunoglobulin-like type 2 receptor alpha. J Virol 83(9):4520–4527. doi:10.1128/JVI.02601-08
Arii J, Goto H, Suenaga T, Oyama M, Kozuka-Hata H, Imai T, Minowa A, Akashi H, Arase H, Kawaoka Y, Kawaguchi Y (2010a) Non-muscle myosin IIA is a functional entry receptor for herpes simplex virus-1. Nature 467(7317):859–862. doi:10.1038/nature09420
Arii J, Wang J, Morimoto T, Suenaga T, Akashi H, Arase H, Kawaguchi Y (2010b) A single-amino-acid substitution in herpes simplex virus 1 envelope glycoprotein B at a site required for binding to the paired immunoglobulin-like type 2 receptor alpha (PILRalpha) abrogates PILRalpha-dependent viral entry and reduces pathogenesis. J Virol 84(20):10773–10783. doi:10.1128/JVI.01166-10
Arii J, Hirohata Y, Kato A, Kawaguchi Y (2015) Nonmuscle myosin heavy chain IIb mediates herpes simplex virus 1 entry. J Virol 89(3):1879–1888. doi:10.1128/JVI.03079-14
Azab W, Osterrieder N (2012) Glycoproteins D of equine herpesvirus type 1 (EHV-1) and EHV-4 determine cellular tropism independently of integrins. J Virol 86(4):2031–2044. doi:10.1128/JVI.06555-11
Azab W, Tsujimura K, Maeda K, Kobayashi K, Mohamed YM, Kato K, Matsumura T, Akashi H (2010) Glycoprotein C of equine herpesvirus 4 plays a role in viral binding to cell surface heparan sulfate. Virus Res 151(1):1–9
Azab W, Zajic L, Osterrieder N (2012) The role of glycoprotein H of equine herpesviruses 1 and 4 (EHV-1 and EHV-4) in cellular host range and integrin binding. Vet Res 43(1):61. doi:10.1186/1297-9716-43-61
Azab W, Lehmann MJ, Osterrieder N (2013) Glycoprotein H and alpha4beta1 integrins determine the entry pathway of alphaherpesviruses. J Virol 87(10):5937–5948. doi:10.1128/JVI.03522-12
Azab W, Harman R, Miller D, Tallmadge R, Frampton AR Jr, Antczak DF, Osterrieder N (2014) Equine herpesvirus type 4 (EHV-4) uses a restricted set of equine major histocompatibility complex class I proteins as entry receptors. J Gen Virol. doi:10.1099/vir.0.066407-0
Azab W, Gramatica A, Herrmann A, Osterrieder N (2015) Binding of alphaherpesvirus glycoprotein H to surface alpha4beta1-integrins activates calcium-signaling pathways and induces phosphatidylserine exposure on the plasma membrane. mBio 6(5):e01552–e01515. doi:10.1128/mBio.01552-15
Backovic M, DuBois RM, Cockburn JJ, Sharff AJ, Vaney MC, Granzow H, Klupp BG, Bricogne G, Mettenleiter TC, Rey FA (2010) Structure of a core fragment of glycoprotein H from pseudorabies virus in complex with antibody. Proc Natl Acad Sci USA 107(52):22635–22640. doi:10.1073/pnas.1011507107
Baldwin J, Antoine TE, Shukla D, Tiwari V (2013) Zebrafish encoded 3-O-sulfotransferase-2 generated heparan sulfate serves as a receptor during HSV-1 entry and spread. Biochem Biophys Res Commun 432(4):672–676. doi:10.1016/j.bbrc.2013.02.020
Banfield BW, Leduc Y, Esford L, Visalli RJ, Brandt CR, Tufaro F (1995) Evidence for an interaction of herpes simplex virus with chondroitin sulfate proteoglycans during infection. Virology 208(2):531–539. doi:10.1006/viro.1995.1184
Berridge MJ (1993) Inositol trisphosphate and calcium signalling. Nature 361(6410):315–325. doi:10.1038/361315a0
Berridge MJ, Bootman MD, Roderick HL (2003) Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol 4(7):517–529. doi:10.1038/nrm1155
Bohm SW, Backovic M, Klupp BG, Rey FA, Mettenleiter TC, Fuchs W (2015) Functional characterization of glycoprotein H chimeras composed of conserved domains of the pseudorabies virus and herpes simplex virus 1 homologs. J Virol 90(1):421–432. doi:10.1128/JVI.01985-15
Campadelli-Fiume G, Menotti L (2007) Entry of alphaherpesviruses into the cell. In: Arvin A, Campadelli-Fiume G, Mocarski E, Moore PS, Roizman B, Whitley R, Yamanishi K (eds) Human herpesviruses: biology, therapy, and immunoprophylaxis. Cambridge University Press, Cambridge
Campadelli-Fiume G, Cocchi F, Menotti L, Lopez M (2000) The novel receptors that mediate the entry of herpes simplex viruses and animal alphaherpesviruses into cells. Rev Med Virol 10(5):305–319
Carfi A, Willis SH, Whitbeck JC, Krummenacher C, Cohen GH, Eisenberg RJ, Wiley DC (2001) Herpes simplex virus glycoprotein D bound to the human receptor HveA. Mol Cell 8(1):169–179
Ch’ng TH, Enquist LW (2005) Neuron-to-cell spread of pseudorabies virus in a compartmented neuronal culture system. J Virol 79(17):10875–10889. doi:10.1128/JVI.79.17.10875-10889.2005
Chen JJ, Zhu Z, Gershon AA, Gershon MD (2004) Mannose 6-phosphate receptor dependence of varicella zoster virus infection in vitro and in the epidermis during varicella and zoster. Cell 119(7):915–926. doi:10.1016/j.cell.2004.11.007
Cheshenko N, Del Rosario B, Woda C, Marcellino D, Satlin LM, Herold BC (2003) Herpes simplex virus triggers activation of calcium-signaling pathways. J Cell Biol 163(2):283–293. doi:10.1083/jcb.200301084jcb.200301084
Cheshenko N, Liu W, Satlin LM, Herold BC (2005) Focal adhesion kinase plays a pivotal role in herpes simplex virus entry. J Biol Chem 280(35):31116–31125. doi:10.1074/jbc.M503518200
Cheshenko N, Liu W, Satlin LM, Herold BC (2007) Multiple receptor interactions trigger release of membrane and intracellular calcium stores critical for herpes simplex virus entry. Mol Biol Cell 18(8):3119–3130. doi:10.1091/mbc.E07-01-0062
Cheshenko N, Trepanier JB, Stefanidou M, Buckley N, Gonzalez P, Jacobs W, Herold BC (2013) HSV activates Akt to trigger calcium release and promote viral entry: novel candidate target for treatment and suppression. FASEB J 27(7):2584–2599. doi:10.1096/fj.12-220285
Cheshenko N, Trepanier JB, Gonzalez PA, Eugenin EA, Jacobs WR Jr, Herold BC (2014) Herpes simplex virus type 2 glycoprotein H interacts with integrin alphavbeta3 to facilitate viral entry and calcium signaling in human genital tract epithelial cells. J Virol 88(17):10026–10038. doi:10.1128/JVI.00725-14
Chowdary TK, Cairns TM, Atanasiu D, Cohen GH, Eisenberg RJ, Heldwein EE (2010) Crystal structure of the conserved herpesvirus fusion regulator complex gH-gL. Nat Struct Mol Biol 17(7):882–888. doi:10.1038/nsmb.1837
Clement C, Tiwari V, Scanlan PM, Valyi-Nagy T, Yue BY, Shukla D (2006) A novel role for phagocytosis-like uptake in herpes simplex virus entry. J Cell Biol 174(7):1009–1021. doi:10.1083/jcb.200509155
Cole NL, Grose C (2003) Membrane fusion mediated by herpesvirus glycoproteins: the paradigm of varicella-zoster virus. Rev Med Virol 13(4):207–222. doi:10.1002/rmv.377
Connolly SA, Whitbeck JJ, Rux AH, Krummenacher C, van Drunen Littel-van den Hurk S, Cohen GH, Eisenberg RJ (2001) Glycoprotein D homologs in herpes simplex virus type 1, pseudorabies virus, and bovine herpes virus type 1 bind directly to human HveC(nectin-1) with different affinities. Virology 280(1):7–18. doi:10.1006/viro.2000.0747
Connolly SA, Landsburg DJ, Carfi A, Wiley DC, Eisenberg RJ, Cohen GH (2002) Structure-based analysis of the herpes simplex virus glycoprotein D binding site present on herpesvirus entry mediator HveA (HVEM). J Virol 76(21):10894–10904
Connolly SA, Landsburg DJ, Carfi A, Wiley DC, Cohen GH, Eisenberg RJ (2003) Structure-based mutagenesis of herpes simplex virus glycoprotein D defines three critical regions at the gD-HveA/HVEM binding interface. J Virol 77(14):8127–8140
Connolly SA, Landsburg DJ, Carfi A, Whitbeck JC, Zuo Y, Wiley DC, Cohen GH, Eisenberg RJ (2005) Potential nectin-1 binding site on herpes simplex virus glycoprotein d. J Virol 79(2):1282–1295
Connolly SA, Jackson JO, Jardetzky TS, Longnecker R (2011) Fusing structure and function: a structural view of the herpesvirus entry machinery. Nat Rev Microbiol 9(5):369–381
Davis GE, Thomas JS, Madden S (1997) The alpha4beta1 integrin can mediate leukocyte adhesion to casein and denatured protein substrates. J Leukoc Biol 62(3):318–328
Davison AJ, Scott JE (1986) The complete DNA sequence of varicella-zoster virus. J Gen Virol 67(Pt 9):1759–1816. doi:10.1099/0022-1317-67-9-1759
Davison AJ, Eberle R, Ehlers B, Hayward GS, McGeoch DJ, Minson AC, Pellett PE, Roizman B, Studdert MJ, Thiry E (2009) The order Herpesvirales. Arch Virol 154(1):171–177
de Jong MA, de Witte L, Bolmstedt A, van Kooyk Y, Geijtenbeek TB (2008) Dendritic cells mediate herpes simplex virus infection and transmission through the C-type lectin DC-SIGN. J Gen Virol 89(Pt 10):2398–2409. doi:10.1099/vir.0.2008/003129-0
De Regge N, Nauwynck HJ, Geenen K, Krummenacher C, Cohen GH, Eisenberg RJ, Mettenleiter TC, Favoreel HW (2006) Alpha-herpesvirus glycoprotein D interaction with sensory neurons triggers formation of varicosities that serve as virus exit sites. J Cell Biol 174(2):267–275. doi:10.1083/jcb.200510156
Di Giovine P, Settembre EC, Bhargava AK, Luftig MA, Lou H, Cohen GH, Eisenberg RJ, Krummenacher C, Carfi A (2011) Structure of herpes simplex virus glycoprotein D bound to the human receptor nectin-1. PLoS Pathog 7(9):e1002277. doi:10.1371/journal.ppat.1002277
Dixit R, Tiwari V, Shukla D (2008) Herpes simplex virus type 1 induces filopodia in differentiated P19 neural cells to facilitate viral spread. Neurosci Lett 440(2):113–118. doi:10.1016/j.neulet.2008.05.031
Dohner K, Nagel CH, Sodeik B (2005) Viral stop-and-go along microtubules: taking a ride with dynein and kinesins. Trends Microbiol 13(7):320–327. doi:10.1016/j.tims.2005.05.010
DuBois RM, Vaney MC, Tortorici MA, Kurdi RA, Barba-Spaeth G, Krey T, Rey FA (2013) Functional and evolutionary insight from the crystal structure of rubella virus protein E1. Nature 493(7433):552–556. doi:10.1038/nature11741
Ellis SA, Martin AJ, Holmes EC, Morrison WI (1995) At least four MHC class I genes are transcribed in the horse: phylogenetic analysis suggests an unusual evolutionary history for the MHC in this species. Eur J Immunogenet 22(3):249–260
Fan Q, Longnecker R (2012) Is nectin-1 the “master” receptor for deadly herpes B virus infection? Virulence 3(4):405. doi:10.4161/viru.20587
Fan Q, Amen M, Harden M, Severini A, Griffiths A, Longnecker R (2012) Herpes B virus utilizes human nectin-1 but not HVEM or PILRalpha for cell-cell fusion and virus entry. J Virol 86(8):4468–4476. doi:10.1128/JVI.00041-12
Favoreel HW, Enquist LW, Feierbach B (2007) Actin and Rho GTPases in herpesvirus biology. Trends Microbiol 15(9):426–433. doi:10.1016/j.tim.2007.08.003
Frampton AR Jr, Goins WF, Cohen JB, von Einem J, Osterrieder N, O’Callaghan DJ, Glorioso JC (2005) Equine herpesvirus 1 utilizes a novel herpesvirus entry receptor. J Virol 79(5):3169–3173
Frampton AR Jr, Stolz DB, Uchida H, Goins WF, Cohen JB, Glorioso JC (2007) Equine herpesvirus 1 enters cells by two different pathways, and infection requires the activation of the cellular kinase ROCK1. J Virol 81(20):10879–10889
Frampton AR, Jr, Uchida H, von Einem J, Goins WF, Grandi P, Cohen JB, Osterrieder N, Glorioso JC (2010) Equine herpesvirus type 1 (EHV-1) utilizes microtubules, dynein, and ROCK1 to productively infect cells. Vet Microbiol 141 (1–2):12–21. doi:10.1016/j.vetmic.2009.07.035
Gabev E, Tobler K, Abril C, Hilbe M, Senn C, Franchini M, Campadelli-Fiume G, Fraefel C, Ackermann M (2010) Glycoprotein D of bovine herpesvirus 5 (BoHV-5) confers an extended host range to BoHV-1 but does not contribute to invasion of the brain. J Virol 84(11):5583–5593. doi:10.1128/JVI.00228-10
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(5369):1618–1620
Gerber SI, Belval BJ, Herold BC (1995) Differences in the role of glycoprotein C of HSV-1 and HSV-2 in viral binding may contribute to serotype differences in cell tropism. Virology 214(1):29–39
Gianni T, Campadelli-Fiume G (2012) αVβ3-integrin relocalizes nectin1 and routes herpes simplex virus to lipid rafts. J Virol 86(5):2850–2855. doi:10.1128/JVI.06689-11
Gianni T, Gatta V, Campadelli-Fiume G (2010) αVβ3-integrin routes herpes simplex virus to an entry pathway dependent on cholesterol-rich lipid rafts and dynamin2. Proc Natl Acad Sci USA 107(51):22260–22265
Gianni T, Salvioli S, Chesnokova LS, Hutt-Fletcher LM, Campadelli-Fiume G (2013) αVβ6- and αVβ8-integrins serve as interchangeable receptors for HSV gH/gL to promote endocytosis and activation of membrane fusion. PLoS Pathog 9(12):e1003806. doi:10.1371/journal.ppat.1003806
Gianni T, Massaro R, Campadelli-Fiume G (2015) Dissociation of HSV gL from gH by αVβ6- or αVβ8-integrin promotes gH activation and virus entry. Proc Natl Acad Sci USA 112(29):E3901–E3910. doi:10.1073/pnas.1506846112
Gilcrease MZ (2007) Integrin signaling in epithelial cells. Cancer Lett 247(1):1–25. doi:10.1016/j.canlet.2006.03.031
Graham KL, Fleming FE, Halasz P, Hewish MJ, Nagesha HS, Holmes IH, Takada Y, Coulson BS (2005) Rotaviruses interact with α4β7 and α4β1 integrins by binding the same integrin domains as natural ligands. J Gen Virol 86(Pt 12):3397–3408
Greber UF (2002) Signalling in viral entry. Cell Mol Life Sci 59(4):608–626
Greenwood AD, Tsangaras K, Ho SY, Szentiks CA, Nikolin VM, Ma G, Damiani A, East ML, Lawrenz A, Hofer H, Osterrieder N (2012) A potentially fatal mix of herpes in zoos. Curr Biol 22(18):1727–1731. doi:10.1016/j.cub.2012.07.035
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(1):93–100
Hahn AS, Desrosiers RC (2014) Binding of the Kaposi’s sarcoma-associated herpesvirus to the ephrin binding surface of the EphA2 receptor and its inhibition by a small molecule. J Virol 88(16):8724–8734. doi:10.1128/JVI.01392-14
Hartman MA, Spudich JA (2012) The myosin superfamily at a glance. J Cell Sci 125(Pt 7):1627–1632. doi:10.1242/jcs.094300
Hay JC (2007) Calcium: a fundamental regulator of intracellular membrane fusion? EMBO Rep 8(3):236–240. doi:10.1038/sj.embor.7400921
Heldwein EE, Krummenacher C (2008) Entry of herpesviruses into mammalian cells. Cell Mol Life Sci 65(11):1653–1668
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(5784):217–220. doi:10.1126/science.1126548
Herold BC, Spear PG (1994) Neomycin inhibits glycoprotein C (gC)-dependent binding of herpes simplex virus type 1 to cells and also inhibits postbinding events in entry. Virology 203(1):166–171
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(3):1090–1098
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(Pt 6):1211–1222
Herold BC, Gerber SI, Belval BJ, Siston AM, Shulman N (1996) Differences in the susceptibility of herpes simplex virus types 1 and 2 to modified heparin compounds suggest serotype differences in viral entry. J Virol 70(6):3461–3469
Hoppe S, Schelhaas M, Jaeger V, Liebig T, Petermann P, Knebel-Morsdorf D (2006) Early herpes simplex virus type 1 infection is dependent on regulated Rac1/Cdc42 signalling in epithelial MDCKII cells. J Gen Virol 87(Pt 12):3483–3494. doi:10.1099/vir.0.82231-0
Hubbard S, Darmani NA, Thrush GR, Dey D, Burnham L, Thompson JM, Jones K, Tiwari V (2010) Zebrafish-encoded 3-O-sulfotransferase-3 isoform mediates herpes simplex virus type 1 entry and spread. Zebrafish 7(2):181–187. doi:10.1089/zeb.2009.0621
Huff JL, Barry PA (2003) B-virus (cercopithecine herpesvirus 1) infection in humans and macaques: potential for zoonotic disease. Emerg Infect Dis 9(2):246–250. doi:10.3201/eid0902.020272
Hutchinson L, Browne H, Wargent V, Davis-Poynter N, Primorac S, Goldsmith K, Minson AC, Johnson DC (1992) A novel herpes simplex virus glycoprotein, gL, forms a complex with glycoprotein H (gH) and affects normal folding and surface expression of gH. J Virol 66(4):2240–2250
Hutt-Fletcher LM, Chesnokova LS (2010) Integrins as triggers of Epstein-Barr virus fusion and epithelial cell infection. Virulence 1(5):395–398. doi:10.4161/viru.1.5.12546
Ivanov AI, Bachar M, Babbin BA, Adelstein RS, Nusrat A, Parkos CA (2007) A unique role for nonmuscle myosin heavy chain IIA in regulation of epithelial apical junctions. PLoS One 2(7):e658. doi:10.1371/journal.pone.0000658
Iyengar S, Hildreth JE, Schwartz DH (1998) Actin-dependent receptor colocalization required for human immunodeficiency virus entry into host cells. J Virol 72(6):5251–5255
Jacquet A, Haumont M, Chellun D, Massaer M, Tufaro F, Bollen A, Jacobs P (1998) The varicella zoster virus glycoprotein B (gB) plays a role in virus binding to cell surface heparan sulfate proteoglycans. Virus Res 53(2):197–207
Kanner SB, Grosmaire LS, Ledbetter JA, Damle NK (1993) Beta 2-integrin LFA-1 signaling through phospholipase C-gamma 1 activation. Proc Natl Acad Sci USA 90(15):7099–7103
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(19):10041–10047. doi:10.1128/JVI.05445-11
Karasneh GA, Shukla D (2011) Herpes simplex virus infects most cell types in vitro: clues to its success. Virol J 8:481. doi:10.1186/1743-422X-8-481
Komoriya A, Green LJ, Mervic M, Yamada SS, Yamada KM, Humphries MJ (1991) The minimal essential sequence for a major cell type-specific adhesion site (CS1) within the alternatively spliced type III connecting segment domain of fibronectin is leucine-aspartic acid-valine. J Biol Chem 266(23):15075–15079
Kopp SJ, Banisadr G, Glajch K, Maurer UE, Grunewald K, Miller RJ, Osten P, Spear PG (2009) Infection of neurons and encephalitis after intracranial inoculation of herpes simplex virus requires the entry receptor nectin-1. Proc Natl Acad Sci USA 106(42):17916–17920. doi:10.1073/pnas.0908892106
Krummenacher C, Nicola AV, Whitbeck JC, Lou H, Hou W, Lambris JD, Geraghty RJ, Spear PG, Cohen GH, Eisenberg RJ (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(9):7064–7074
Krummenacher C, Baribaud F, Ponce de Leon M, Baribaud I, Whitbeck JC, Xu R, Cohen GH, Eisenberg RJ (2004) Comparative usage of herpesvirus entry mediator a and nectin-1 by laboratory strains and clinical isolates of herpes simplex virus. Virology 322(2):286–299
Krummenacher C, Carfi A, Eisenberg RJ, Cohen GH (2013) Entry of herpesviruses into cells: the enigma variations. Adv Exp Med Biol 790:178–195. doi:10.1007/978-1-4614-7651-1_10
Kurtz BM, Singletary LB, Kelly SD, Frampton AR Jr (2010) Equus caballus major histocompatibility complex class I is an entry receptor for equine herpesvirus type 1. J Virol 84(18):9027–9034
Laquerre S, Argnani R, Anderson DB, Zucchini S, Manservigi R, Glorioso JC (1998) Heparan sulfate proteoglycan binding by herpes simplex virus type 1 glycoproteins B and C, which differ in their contributions to virus attachment, penetration, and cell-to-cell spread. J Virol 72(7):6119–6130
Lehmann MJ, Sherer NM, Marks CB, Pypaert M, Mothes W (2005) Actin- and myosin-driven movement of viruses along filopodia precedes their entry into cells. J Cell Biol 170(2):317–325. doi:10.1083/jcb.200503059
Li Q, Ali MA, Cohen JI (2006) Insulin degrading enzyme is a cellular receptor mediating varicella-zoster virus infection and cell-to-cell spread. Cell 127(2):305–316. doi:10.1016/j.cell.2006.08.046
Liang XP, Babiuk LA, van Drunen Littel-van den Hurk S, Fitzpatrick DR, Zamb TJ (1991) Bovine herpesvirus 1 attachment to permissive cells is mediated by its major glycoproteins gI, gIII, and gIV. J Virol 65(3):1124–1132
Linehan MM, Richman S, Krummenacher C, Eisenberg RJ, Cohen GH, Iwasaki A (2004) In vivo role of nectin-1 in entry of herpes simplex virus type 1 (HSV-1) and HSV-2 through the vaginal mucosa. J Virol 78(5):2530–2536
Lopez M, Cocchi F, Menotti L, Avitabile E, Dubreuil P, Campadelli-Fiume G (2000) Nectin2alpha (PRR2alpha or HveB) and nectin2delta are low-efficiency mediators for entry of herpes simplex virus mutants carrying the Leu25Pro substitution in glycoprotein D. J Virol 74(3):1267–1274
Lu W, Seeholzer SH, Han M, Arnold AS, Serrano M, Garita B, Philp NJ, Farthing C, Steele P, Chen J, Linask KK (2008) Cellular nonmuscle myosins NMHC-IIA and NMHC-IIB and vertebrate heart looping. Dev Dyn 237(12):3577–3590. doi:10.1002/dvdy.21645
Lycke E, Johansson M, Svennerholm B, Lindahl U (1991) Binding of herpes simplex virus to cellular heparan sulphate, an initial step in the adsorption process. J Gen Virol 72(Pt 5):1131–1137
Lyman MG, Enquist LW (2009) Herpesvirus interactions with the host cytoskeleton. J Virol 83(5):2058–2066. doi:10.1128/Jvi.01718-08
Mardberg K, Trybala E, Glorioso JC, Bergstrom T (2001) Mutational analysis of the major heparan sulfate-binding domain of herpes simplex virus type 1 glycoprotein C. J Gen Virol 82(Pt 8):1941–1950. doi:10.1099/0022-1317-82-8-1941
Mercer J, Schelhaas M, Helenius A (2010) Virus entry by endocytosis. Annu Rev Biochem 79:803–833. doi:10.1146/annurev-biochem-060208-104626
Mettenleiter TC, Zsak L, Zuckermann F, Sugg N, Kern H, Ben-Porat T (1990) Interaction of glycoprotein gIII with a cellular heparinlike substance mediates adsorption of pseudorabies virus. J Virol 64(1):278–286
Mikoshiba K, Hattori M (2000) IP3 receptor-operated calcium entry. Sci STKE signal transduction knowledge environment 2000 (51):pe1. doi:10.1126/stke.2000.51.pe1
Mizoguchi A, Nakanishi H, Kimura K, Matsubara K, Ozaki-Kuroda K, Katata T, Honda T, Kiyohara Y, Heo K, Higashi M, Tsutsumi T, Sonoda S, Ide C, Takai Y (2002) Nectin: an adhesion molecule involved in formation of synapses. J Cell Biol 156(3):555–565. doi:10.1083/jcb.200103113
Mo C, Lee J, Sommer M, Grose C, Arvin AM (2002) The requirement of varicella zoster virus glycoprotein E (gE) for viral replication and effects of glycoprotein I on gE in melanoma cells. Virology 304(2):176–186
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(3):427–436
Mousseau DD, Banville D, L’Abbe D, Bouchard P, Shen SH (2000) PILRalpha, a novel immunoreceptor tyrosine-based inhibitory motif-bearing protein, recruits SHP-1 upon tyrosine phosphorylation and is paired with the truncated counterpart PILRbeta. J Biol Chem 275(6):4467–4474
O’Donnell CD, Shukla D (2008) The importance of heparan sulfate in herpesvirus infection. Virol Sin 23(6):383–393. doi:10.1007/s12250-008-2992-1
Oh MJ, Akhtar J, Desai P, Shukla D (2010) A role for heparan sulfate in viral surfing. Biochem Biophys Res Commun 391(1):176–181. doi:10.1016/j.bbrc.2009.11.027
Okazaki K, Matsuzaki T, Sugahara Y, Okada J, Hasebe M, Iwamura Y, Ohnishi M, Kanno T, Shimizu M, Honda E et al (1991) BHV-1 adsorption is mediated by the interaction of glycoprotein gIII with heparinlike moiety on the cell surface. Virology 181(2):666–670
Osterrieder N (1999) Construction and characterization of an equine herpesvirus 1 glycoprotein C negative mutant. Virus Res 59(2):165–177
Pellet P, Roizman B (2007) The family Herpesviridae: a brief introduction. In: Fields BN, Knipe DM, Howley PM (eds) Fields virology, 5th edn. Lippincott Williams & Wilkins, Philadelphia, pp 2479–2499
Perelygina L, Patrusheva I, Vasireddi M, Brock N, Hilliard J (2015) B virus (Macacine herpesvirus 1) glycoprotein D is functional but dispensable for virus entry into macaque and human skin cells. J Virol 89(10):5515–5524. doi:10.1128/JVI.03568-14
Petermann P, Haase I, Knebel-Morsdorf D (2009) Impact of Rac1 and Cdc42 signaling during early herpes simplex virus type 1 infection of keratinocytes. J Virol 83(19):9759–9772. doi:10.1128/JVI.00835-09
Petermann P, Rahn E, Thier K, Hsu MJ, Rixon FJ, Kopp SJ, Knebel-Morsdorf D (2015a) Role of nectin-1 and herpesvirus entry mediator as cellular receptors for herpes simplex virus 1 on primary murine dermal fibroblasts. J Virol 89(18):9407–9416. doi:10.1128/JVI.01415-15
Petermann P, Thier K, Rahn E, Rixon FJ, Bloch W, Ozcelik S, Krummenacher C, Barron MJ, Dixon MJ, Scheu S, Pfeffer K, Knebel-Morsdorf D (2015b) Entry mechanisms of herpes simplex virus 1 into murine epidermis: involvement of nectin-1 and herpesvirus entry mediator as cellular receptors. J Virol 89(1):262–274. doi:10.1128/JVI.02917-14
Pontow SE, Heyden NV, Wei S, Ratner L (2004) Actin cytoskeletal reorganizations and coreceptor-mediated activation of rac during human immunodeficiency virus-induced cell fusion. J Virol 78(13):7138–7147. doi:10.1128/JVI.78.13.7138-7147.2004
Quarles RH (2007) Myelin-associated glycoprotein (MAG): past, present and beyond. J Neurochem 100(6):1431–1448. doi:10.1111/j.1471-4159.2006.04319.x
Rawat SS, Viard M, Gallo SA, Rein A, Blumenthal R, Puri A (2003) Modulation of entry of enveloped viruses by cholesterol and sphingolipids (review). Mol Membr Biol 20(3):243–254. doi:10.1080/0968768031000104944
Rhee SG (2001) Regulation of phosphoinositide-specific phospholipase C. Annu Rev Biochem 70:281–312. doi:10.1146/annurev.biochem.70.1.281
Roizman B (1996) Herpesviridae. In: Field BN, Knipe DM, Howley PM, Channock RM, Melnick JL, Monath TP, Roizman B, Straus SE (eds) Virology, 3rd edn. Lippincott-Raven, Philadelphia, NY
Sakisaka T, Taniguchi T, Nakanishi H, Takahashi K, Miyahara M, Ikeda W, Yokoyama S, Peng YF, Yamanishi K, Takai Y (2001) Requirement of interaction of nectin-1alpha/HveC with afadin for efficient cell-cell spread of herpes simplex virus type 1. J Virol 75(10):4734–4743. doi:10.1128/JVI.75.10.4734-4743.2001
Sakisaka T, Ikeda W, Ogita H, Fujita N, Takai Y (2007) The roles of nectins in cell adhesions: cooperation with other cell adhesion molecules and growth factor receptors. Curr Opin Cell Biol 19(5):593–602. doi:10.1016/j.ceb.2007.09.007
Sarrazin S, Lamanna WC, Esko JD (2011) Heparan sulfate proteoglycans. Cold Spring Harb Perspect Biol 3(7). doi:10.1101/cshperspect.a004952
Sasaki M, Hasebe R, Makino Y, Suzuki T, Fukushi H, Okamoto M, Matsuda K, Taniyama H, Sawa H, Kimura T (2011) Equine major histocompatibility complex class I molecules act as entry receptors that bind to equine herpesvirus-1 glycoprotein D. Genes Cells 16(4):343–357
Satoh T, Arii J, Suenaga T, Wang J, Kogure A, Uehori J, Arase N, Shiratori I, Tanaka S, Kawaguchi Y, Spear PG, Lanier LL, Arase H (2008) PILRalpha is a herpes simplex virus-1 entry coreceptor that associates with glycoprotein B. Cell 132(6):935–944
Schreurs C, Mettenleiter TC, Zuckermann F, Sugg N, Ben-Porat T (1988) Glycoprotein gIII of pseudorabies virus is multifunctional. J Virol 62(7):2251–2257
Sekiya F, Poulin B, Kim YJ, Rhee SG (2004) Mechanism of tyrosine phosphorylation and activation of phospholipase C-gamma 1. Tyrosine 783 phosphorylation is not sufficient for lipase activation. J Biol Chem 279(31):32181–32190. doi:10.1074/jbc.M405116200M405116200
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(5):1273–1281
Shukla D, Spear PG (2001) Herpesviruses and heparan sulfate: an intimate relationship in aid of viral entry. J Clin Invest 108(4):503–510. doi:10.1172/JCI13799
Shukla D, Liu J, Blaiklock P, Shworak NW, Bai X, Esko JD, Cohen GH, Eisenberg RJ, Rosenberg RD, Spear PG (1999) A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry. Cell 99(1):13–22
Spear PG (1993) Entry of alphaherpesviruses into cells. Semin Virol 4:167–180
Spear PG (2004) Herpes simplex virus: receptors and ligands for cell entry. Cell Microbiol 6(5):401–410
Spear PG, Longnecker R (2003) Herpesvirus entry: an update. J Virol 77(19):10179–10185
Spear PG, Eisenberg RJ, Cohen GH (2000) Three classes of cell surface receptors for alphaherpesvirus entry. Virology 275(1):1–8. doi:10.1006/viro.2000.0529
Suenaga T, Satoh T, Somboonthum P, Kawaguchi Y, Mori Y, Arase H (2010) Myelin-associated glycoprotein mediates membrane fusion and entry of neurotropic herpesviruses. Proc Natl Acad Sci USA 107(2):866–871. doi:10.1073/pnas.0913351107
Suenaga T, Matsumoto M, Arisawa F, Kohyama M, Hirayasu K, Mori Y, Arase H (2015) Sialic acids on varicella-zoster virus glycoprotein B are required for cell-cell fusion. J Biol Chem 290(32):19833–19843. doi:10.1074/jbc.M114.635508
Takada Y, Ye X, Simon S (2007) The integrins. Genome Biol 8(5):215
Tallmadge RL, Lear TL, Antczak DF (2005) Genomic characterization of MHC class I genes of the horse. Immunogenetics 57(10):763–774. doi:10.1007/s00251-005-0034-9
Tallmadge RL, Campbell JA, Miller DC, Antczak DF (2010) Analysis of MHC class I genes across horse MHC haplotypes. Immunogenetics 62(3):159–172. doi:10.1007/s00251-009-0420-9
Tan X, Brunovskis P, Velicer LF (2001) Transcriptional analysis of Marek’s disease virus glycoprotein D, I, and E genes: gD expression is undetectable in cell culture. J Virol 75(5):2067–2075. doi:10.1128/JVI.75.5.2067-2075.2001
Taylor JM, Lin E, Susmarski N, Yoon M, Zago A, Ware CF, Pfeffer K, Miyoshi J, Takai Y, Spear PG (2007) Alternative entry receptors for herpes simplex virus and their roles in disease. Cell Host Microbe 2(1):19–28. doi:10.1016/j.chom.2007.06.005
Tiwari V, Shukla D (2010) Phosphoinositide 3 kinase signalling may affect multiple steps during herpes simplex virus type-1 entry. J Gen Virol 91(Pt 12):3002–3009. doi:10.1099/vir.0.024166-0
Tiwari V, Clement C, Xu D, Valyi-Nagy T, Yue BY, Liu J, Shukla D (2006) Role for 3-O-sulfated heparan sulfate as the receptor for herpes simplex virus type 1 entry into primary human corneal fibroblasts. J Virol 80(18):8970–8980. doi:10.1128/JVI.00296-06
Trybala E, Liljeqvist JA, Svennerholm B, Bergstrom T (2000) Herpes simplex virus types 1 and 2 differ in their interaction with heparan sulfate. J Virol 74(19):9106–9114
Van den Broeke C, Favoreel HW (2011) Actin’ up: herpesvirus interactions with Rho GTPase signaling. Viruses 3(4):278–292. doi:10.3390/v3040278
Van Seventer GA, Bonvini E, Yamada H, Conti A, Stringfellow S, June CH, Shaw S (1992) Costimulation of T cell receptor/CD3-mediated activation of resting human CD4+ T cells by leukocyte function-associated antigen-1 ligand intercellular cell adhesion molecule-1 involves prolonged inositol phospholipid hydrolysis and sustained increase of intracellular Ca2+ levels. J Immunol 149(12):3872–3880
Veettil MV, Bandyopadhyay C, Dutta D, Chandran B (2014) Interaction of KSHV with host cell surface receptors and cell entry. Viruses 6(10):4024–4046. doi:10.3390/v6104024
Vicente-Manzanares M, Ma X, Adelstein RS, Horwitz AR (2009) Non-muscle myosin II takes centre stage in cell adhesion and migration. Nat Rev Mol Cell Biol 10(11):778–790. doi:10.1038/nrm2786
Wang J, Fan Q, Satoh T, Arii J, Lanier LL, Spear PG, Kawaguchi Y, Arase H (2009) Binding of herpes simplex virus glycoprotein B (gB) to paired immunoglobulin-like type 2 receptor alpha depends on specific sialylated O-linked glycans on gB. J Virol 83(24):13042–13045. doi:10.1128/JVI.00792-09
Warner MS, Geraghty RJ, Martinez WM, Montgomery RI, Whitbeck JC, Xu R, Eisenberg RJ, Cohen GH, Spear PG (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(1):179–189
Wohlsein P, Lehmbecker A, Spitzbarth I, Algermissen D, Baumgartner W, Boer M, Kummrow M, Haas L, Grummer B (2011) Fatal epizootic equine herpesvirus 1 infections in new and unnatural hosts. Vet Microbiol 149(3–4):456–460. doi:10.1016/j.vetmic.2010.11.024
WuDunn D, Spear PG (1989) Initial interaction of herpes simplex virus with cells is binding to heparan sulfate. J Virol 63(1):52–58
Yakoub AM, Rawal N, Maus E, Baldwin J, Shukla D, Tiwari V (2014) Comprehensive analysis of herpes simplex virus 1 (HSV-1) entry mediated by zebrafish 3-O-sulfotransferase isoforms: implications for the development of a zebrafish model of HSV-1 infection. J Virol 88(21):12915–12922. doi:10.1128/JVI.02071-14
Yamada E, McVicar DW (2008) Paired receptor systems of the innate immune system. Curr Protoc Immunol (edited by John E Coligan et al, Chap. 1: Appendix 1X). doi:10.1002/0471142735.ima01xs81
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(17):9221–9231
Zhou Y, Frey TK, Yang JJ (2009) Viral calciomics: interplays between Ca2+ and virus. Cell Calcium 46(1):1–17. doi:10.1016/j.ceca.2009.05.005
Zhu Z, Gershon MD, Ambron R, Gabel C, Gershon AA (1995) Infection of cells by varicella zoster virus: inhibition of viral entry by mannose 6-phosphate and heparin. Proc Natl Acad Sci USA 92(8):3546–3550
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Azab, W., Osterrieder, K. (2017). Initial Contact: The First Steps in Herpesvirus Entry. In: Osterrieder, K. (eds) Cell Biology of Herpes Viruses. Advances in Anatomy, Embryology and Cell Biology, vol 223. Springer, Cham. https://doi.org/10.1007/978-3-319-53168-7_1
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