1887

Abstract

Herpes simplex virus type 1 (HSV-1) enters its host via epithelia and spreads to neuronal cells where latency is established. Hence, the route of infection relies on penetration and subsequent passage of HSV-1 through highly polarized cells. Infection studies were performed in both polarized MDCKII cells and primary human keratinocytes to gain insight into the pathway of virus entry into individual epithelial cells. Early viral gene expression was barely detectable in confluent MDCKII cells, even at high m.o.i. However, after wounding the cell layer, infected cells were observed next to the wound, where basolateral membranes were accessible. In subconfluent monolayers, MDCKII cells are organized in islets. After infection, viral capsids and early viral gene expression were detectable in peripheral cells of islets, supporting virus penetration via basolateral membranes. Further infection studies were performed in human keratinocytes, which represent the primary target cells for HSV-1 infection . In primary keratinocytes grown as monolayer cultures and wounded prior to infection, HSV-1 infection led to early viral gene expression predominantly in cells next to the wound. When stratifying cultures of primary human keratinocytes were infected, early viral gene expression was localized to peripheral cells of basal keratinocytes. Finally, infection of epithelial tissue such as human foreskin epithelia demonstrated HSV-1 entry exclusively via basal cell layers. Staining of the potential coreceptor nectin-1/HveC revealed no correlation of receptor localization and virus entry sites in keratinocytes. These results provide first evidence for a virus entry mechanism that relies on the accessibility to basal surfaces of epithelial tissue and to basolateral membranes, both in MDCKII and primary keratinocytes.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.19226-0
2003-09-01
2020-07-10
Loading full text...

Full text loading...

/deliver/fulltext/jgv/84/9/vir842473.html?itemId=/content/journal/jgv/10.1099/vir.0.19226-0&mimeType=html&fmt=ahah

References

  1. Aberle H., Schwartz H., Kemler R.. 1996; Cadherin–catenin complex: protein interactions and their implications for cadherin function. J Cell Biochem61:514–523
    [Google Scholar]
  2. Blau D. M., Compans R. W.. 1996; Polarization of viral entry and release in epithelial cells. Semin Virol7:245–253
    [Google Scholar]
  3. 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 Virol10:305–319
    [Google Scholar]
  4. Cocchi F., Menotti L., Mirandola P., Lopez M., Campadelli-Fiume G.. 1998; The ectodomain of a novel member of the immunoglobulin subfamily related to the poliovirus receptor has the attributes of a bona fide receptor for herpes simplex virus types 1 and 2 in human cells. J Virol72:9992–10002
    [Google Scholar]
  5. de Bruyn Kops A., Knipe D. M.. 1988; Formation of DNA replication structures in herpes virus-infected cells requires a viral DNA binding protein. Cell55:857–868
    [Google Scholar]
  6. Everett R. D.. 2000; ICPO, a regulator of herpes simplex virus during lytic and latent infection. Bioessays22:761–770
    [Google Scholar]
  7. Everett R. D., Cross A., Orr A.. 1993; A truncated form of herpes simplex virus type 1 immediate-early protein Vmw110 is expressed in a cell type dependent manner. Virology197:751–756
    [Google Scholar]
  8. Geraghty R. J., Krummenacher C., Cohen G. H., Eisenberg R. J., Spear P. G.. 1998; Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and poliovirus receptor. Science280:1618–1620
    [Google Scholar]
  9. Gonzalez-Mariscal L., Betanzos A., Avila-Flores A.. 2000; MAGUK proteins: structure and role in the tight junction. Semin Cell Dev Biol11:315–324
    [Google Scholar]
  10. Gottardi C. J., Arpin M., Fanning A. S., Louvard D.. 1996; The junction-associated protein, zonula occludens-1, localizes to the nucleus before the maturation and during the remodeling of cell–cell contacts. Proc Natl Acad Sci U S A93:10779–10784
    [Google Scholar]
  11. Hansson G. C., Simons K., van Meer G.. 1986; Two strains of the Madin–Darby canine kidney (MDCK) cell line have distinct glycosphingolipid compositions. EMBO J5:483–489
    [Google Scholar]
  12. Hayashi K.. 1995; Role of tight junctions of polarized epithelial MDCK cells in the replication of herpes simplex virus type 1. J Med Virol47:323–329
    [Google Scholar]
  13. Herold B. C., Visalli R. J., Susmarski N., Brandt C. R., Spear P. G.. 1994; Glycoprotein C-independent binding of herpes simplex virus to cells requires cell surface heparan sulphate and glycoprotein B. J Gen Virol75:1211–1222
    [Google Scholar]
  14. Huber M. T., Wisner T. W., Hegde N. R.. 7 other authors 2001; Herpes simplex virus with highly reduced gD levels can efficiently enter and spread between human keratinocytes. J Virol75:10309–10318
    [Google Scholar]
  15. Hukkanen V., Mikola H., Nykanen M., Syrjänen S.. 1999; Herpes simplex virus type 1 infection has two separate modes of spread in three-dimensional keratinocyte culture. J Gen Virol80:2149–2155
    [Google Scholar]
  16. Krummenacher C., Baribaud I., Ponce de Leon M., Whitbeek J. C., Lou H., Cohen G. H., Eisenberg R. J.. 2000; Localization of a binding site for herpes simplex virus glycoprotein D on herpesvirus entry mediator C by using antireceptor monoclonal antibodies. J Virol74:10863–10872
    [Google Scholar]
  17. Louvard D.. 1980; Apical membrane aminopeptidase appears at site of cell–cell contact in cultured kidney epithelial cells. Proc Natl Acad Sci U S A77:4132–4136
    [Google Scholar]
  18. Maul G. G., Guldner H. H., Spivack J. G.. 1993; Modification of discrete nuclear domains induced by herpes simplex virus type 1 immediate early gene 1 product (ICP0. J Gen Virol74:2679–2690
    [Google Scholar]
  19. McClelland D. A., Aitken J. D., Bhella D., McNab D., Mitchell J., Kelly S. M., Price N. C., Rixon F. J.. 2002; pH reduction as a trigger for dissociation of herpes simplex virus type 1 scaffolds. J Virol76:7407–7417
    [Google Scholar]
  20. McGeoch D. J., Dalrymple M. A., Davison A. J., Dolan A., Frame M. C., McNab D., Perry L. J., Scott J. E., Taylor P.. 1988; The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1. J Gen Virol69:1531–1574
    [Google Scholar]
  21. Nolte C. J., Oleson M. A., Bilbo P. R., Parenteau N. L.. 1993; Development of a stratum corneum and barrier function in an organotypic skin culture. Arch Dermatol Res285:466–474
    [Google Scholar]
  22. Parkinson J., Everett R. D.. 2000; Alphaherpesvirus proteins related to herpes simplex virus type 1 ICPO affect cellular structures and proteins. J Virol74:10006–10017
    [Google Scholar]
  23. Sears A. E., McGwire B. S., Roizman B.. 1991; Infection of polarized MDCK cells with herpes simplex virus 1: two asymmetrically distributed cell receptors interact with different viral proteins. Proc Natl Acad Sci U S A88:5087–5091
    [Google Scholar]
  24. Simons K., Fuller S. D.. 1985; Cell surface polarity in epithelia. Annu Rev Cell Biol1:243–288
    [Google Scholar]
  25. Spear P. G.. 1993; Entry of alphaherpesviruses into cells. Semin Virol4:167–180
    [Google Scholar]
  26. Spear P. G., Eisenberg R. J., Cohen G. H.. 2000; Three classes of cell surface receptors for alphaherpesvirus entry. Virology275:1–8
    [Google Scholar]
  27. Syrjänen S., Mikola H., Nykanen M., Hukkanen V.. 1996; In vitro establishment of lytic and nonproductive infection by herpes simplex virus type 1 in three-dimensional keratinocyte culture. J Virol70:6524–6528
    [Google Scholar]
  28. Takai Y., Nakanishi H.. 2002; Nectin and afadin: novel organizers of intercellular junctions. J Cell Sci116:17–27
    [Google Scholar]
  29. Topp K. S., Rothman A. L., Lavail J. H.. 1997; Herpes virus infection of RPE and MDCK cells: polarity of infection. Exp Eye Res64:343–354
    [Google Scholar]
  30. Tran L. C., Kissner J. M., Westerman L. E., Sears A. E.. 2000; A herpes simplex virus 1 recombinant lacking the glycoprotein G coding sequences is defective in entry through apical surfaces of polarized epithelial cells in culture and in vivo . Proc Natl Acad Sci U S A97:1818–1822
    [Google Scholar]
  31. Visalli R. J., Courtney R. J., Meyers C.. 1997; Infection and replication of herpes simplex virus type 1 in an organotypic epithelial culture system. Virology230:236–243
    [Google Scholar]
  32. Watt F. M.. 1998; Cultivation of human epidermal keratinocytes with a 3T3 feeder layer. In Cell Biology: a Laboratory Handbook pp 113–118 Edited by Celis J. E.. London: Academic Press;
    [Google Scholar]
  33. WuDunn D., Spear P. G.. 1989; Initial interaction of herpes simplex virus with cells is binding to heparan sulfate. J Virol63:52–58
    [Google Scholar]
  34. Yoon M., Spear P. G.. 2002; Disruption of adherens junctions liberates nectin-1 to serve as receptor for herpes simplex virus and pseudorabies virus entry. J Virol76:7203–7208
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.19226-0
Loading
/content/journal/jgv/10.1099/vir.0.19226-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

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