Skip to content
1887

Journal of General Virology header logo Journal of General Virology

Volume 92, Issue 10

Restrictions that control herpes simplex virus type 1 infection in mouse brain No Access

Abstract

Elucidating the cellular and molecular factors governing herpes simplex virus type 1 (HSV-1) neurotropism is a prerequisite for understanding HSV-1 encephalitis and for targeting HSV-1-derived vectors for gene transfer to the brain. Earlier we had described an system of mouse brain slices and demonstrated a selective and unique infection pattern, mostly around the ventricles. Here, we examined tissue factors controlling HSV-1 infection of brain slices. We demonstrated that heparan sulphate, while an important factor, does not determine the infection pattern. Hyaluronic acid, but not collagen, appears to enhance HSV-1 brain infection. To investigate whether tissue distribution of viral receptors determines the infection pattern, we examined transcription of herpes virus entry mediator and nectin-1 receptor genes in infected and uninfected brain regions. Both the infected and the uninfected regions express the receptors. We also explored the influence of intra-cellular factors. HSV-1 does not preferentially infect proliferating cells in the brain slices, despite its predilection to the ventricular zones. To delineate the step at which the HSV-1 infection cascade is restricted, mRNA was isolated following tissue infection, and transcription of the immediate-early and late viral genes was evaluated. The results indicated that HSV-1 genes are not expressed in regions that do not express a viral reporter gene. Therefore, we conclude that tissue resistance to infection is associated with a block at or prior to the immediate-early mRNA synthesis. Taken together, using the system of organotypic culture we describe here extra-cellular and intra-cellular restriction levels of HSV-1 brain infection.

  • Received:
  • Accepted:
  • Published Online:
© 2011 SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.031013-0
2011-10-01
2025-04-19
Loading full text...

Full text loading...

References

  1. Alian A., Sela-Donenfeld D., Panet A., Eldor A. 2000; Avian hemangioma retrovirus induces cell proliferation via the envelope (env) gene. Virology 276:161–168 [View Article][PubMed]
     [Google Scholar]
  2. Banfield B. W., Leduc Y., Esford L., Visalli R. J., Brandt C. R., Tufaro F. 1995; Evidence for an interaction of herpes simplex virus with chondroitin sulfate proteoglycans during infection. Virology 208:531–539 [View Article][PubMed]
     [Google Scholar]
  3. Barnett E. M., Jacobsen G., Evans G., Cassell M., Perlman S. 1994; Herpes simplex encephalitis in the temporal cortex and limbic system after trigeminal nerve inoculation. J Infect Dis 169:782–786 [View Article][PubMed]
     [Google Scholar]
  4. Ben-Hur T., Rösen-Wolff A., Lamade W., Darai G., Becker Y. 1988; HSV-1 DNA sequence determining intraperitoneal pathogenicity in mice is required for transcription of viral immediate-early genes in macrophages. Virology 163:397–404 [View Article][PubMed]
     [Google Scholar]
  5. Berges B. K., Wolfe J. H., Fraser N. W. 2007; Transduction of brain by herpes simplex virus vectors. Mol Ther 15:20–29 [View Article][PubMed]
     [Google Scholar]
  6. Bergström T., Conradi N., Hansson E., Liljeroth A., Vahlne A. 1994; Resistance of rat CNS to brain stem infection with herpes simplex virus type 1. Acta Neuropathol 87:398–404 [View Article][PubMed]
     [Google Scholar]
  7. Bradford M. M. 1976; A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254 [View Article][PubMed]
     [Google Scholar]
  8. Braun E., Zimmerman T., Hur T. B., Reinhartz E., Fellig Y., Panet A., Steiner I. 2006; Neurotropism of herpes simplex virus type 1 in brain organ cultures. J Gen Virol 87:2827–2837 [View Article][PubMed]
     [Google Scholar]
  9. Chakrabarti S., Brechling K., Moss B. 1985; Vaccinia virus expression vector: coexpression of beta-galactosidase provides visual screening of recombinant virus plaques. Mol Cell Biol 5:3403–3409[PubMed]
     [Google Scholar]
  10. Cho E. S., Lee S. Y., Park J. Y., Hong S. G., Ryu P. D. 2007; Organotypic slice culture of the hypothalamic paraventricular nucleus of rat. J Vet Sci 8:15–20 [View Article][PubMed]
     [Google Scholar]
  11. Chrisp C. E., Sunstrum J. C., Averill D. R. Jr, Levine M., Glorioso J. C. 1989; Characterization of encephalitis in adult mice induced by intracerebral inoculation of herpes simplex virus type 1 (KOS) and comparison with mutants showing decreased virulence. Lab Invest 60:822–830[PubMed]
     [Google Scholar]
  12. Conrady C. D., Drevets D. A., Carr D. J. 2010; Herpes simplex type I (HSV-1) infection of the nervous system: is an immune response a good thing?. J Neuroimmunol 220:1–9 [View Article][PubMed]
     [Google Scholar]
  13. Corner M. A., Baker R. E., van Pelt J., Wolters P. S. 2005; Compensatory physiological responses to chronic blockade of amino acid receptors during early development in spontaneously active organotypic cerebral cortex explants cultured in vitro . Prog Brain Res 147:231–248 [View Article][PubMed]
     [Google Scholar]
  14. Deepa S. S., Carulli D., Galtrey C., Rhodes K., Fukuda J., Mikami T., Sugahara K., Fawcett J. W. 2006; Composition of perineuronal net extracellular matrix in rat brain: a different disaccharide composition for the net-associated proteoglycans. J Biol Chem 281:17789–17800 [View Article][PubMed]
     [Google Scholar]
  15. Desai P., Person S. 1998; Incorporation of the green fluorescent protein into the herpes simplex virus type 1 capsid. J Virol 72:7563–7568[PubMed]
     [Google Scholar]
  16. Diwan P., Lacasse J. J., Schang L. M. 2004; Roscovitine inhibits activation of promoters in herpes simplex virus type 1 genomes independently of promoter-specific factors. J Virol 78:9352–9365 [View Article][PubMed]
     [Google Scholar]
  17. Esko J. D., Lindahl U. 2001; Molecular diversity of heparan sulfate. J Clin Invest 108:169–173[PubMed] [CrossRef]
     [Google Scholar]
  18. Favre D., Cherel Y., Provost N., Blouin V., Ferry N., Moullier P., Salvetti A. 2000; Hyaluronidase enhances recombinant adeno-associated virus (rAAV)-mediated gene transfer in the rat skeletal muscle. Gene Ther 7:1417–1420 [View Article][PubMed]
     [Google Scholar]
  19. Frederiksen K., McKay R. D. 1988; Proliferation and differentiation of rat neuroepithelial precursor cells in vivo . J Neurosci 8:1144–1151[PubMed]
     [Google Scholar]
  20. Hasson E., Slovatizky Y., Shimoni Y., Falk H., Panet A., Mitrani E. 2005; Solid tissues can be manipulated ex vivo and used as vehicles for gene therapy. J Gene Med 7:926–935 [View Article][PubMed]
     [Google Scholar]
  21. Heldwein E. E., Krummenacher C. 2008; Entry of herpesviruses into mammalian cells. Cell Mol Life Sci 65:1653–1668 [View Article][PubMed]
     [Google Scholar]
  22. Honigman A., Zeira E., Ohana P., Abramovitz R., Tavor E., Bar I., Zilberman Y., Rabinovsky R., Gazit D. et al. other authors 2001; Imaging transgene expression in live animals. Mol Ther 4:239–249 [View Article][PubMed]
     [Google Scholar]
  23. Hoppe S., Schelhaas M., Jaeger V., Liebig T., Petermann P., Knebel-Mörsdorf D. 2006; Early herpes simplex virus type 1 infection is dependent on regulated Rac1/Cdc42 signalling in epithelial MDCKII cells. J Gen Virol 87:3483–3494 [View Article][PubMed]
     [Google Scholar]
  24. House S. B., Thomas A., Kusano K., Gainer H. 1998; Stationary organotypic cultures of oxytocin and vasopressin magnocellular neurones from rat and mouse hypothalamus. J Neuroendocrinol 10:849–861 [View Article][PubMed]
     [Google Scholar]
  25. Hubert T., Grimal S., Carroll P., Fichard-Carroll A. 2009; Collagens in the developing and diseased nervous system. Cell Mol Life Sci 66:1223–1238 [View Article][PubMed]
     [Google Scholar]
  26. Immergluck L. C., Domowicz M. S., Schwartz N. B., Herold B. C. 1998; Viral and cellular requirements for entry of herpes simplex virus type 1 into primary neuronal cells. J Gen Virol 79:549–559[PubMed]
     [Google Scholar]
  27. Karthikeyan L., Flad M., Engel M., Meyer-Puttlitz B., Margolis R. U., Margolis R. K. 1994; Immunocytochemical and in situ hybridization studies of the heparan sulfate proteoglycan, glypican, in nervous tissue. J Cell Sci 107:3213–3222[PubMed]
     [Google Scholar]
  28. Kawasaki H., Kosugi I., Arai Y., Tsutsui Y. 2002; The amount of immature glial cells in organotypic brain slices determines the susceptibility to murine cytomegalovirus infection. Lab Invest 82:1347–1358[PubMed] [CrossRef]
     [Google Scholar]
  29. Kennedy P. G., Clements G. B., Brown S. M. 1983; Differential susceptibility of human neural cell types in culture to infection with herpes simplex virus. Brain 106:101–119 [View Article][PubMed]
     [Google Scholar]
  30. Kolodkin-Gal D., Zamir G., Edden Y., Pikarsky E., Pikarsky A., Haim H., Haviv Y. S., Panet A. 2008; Herpes simplex virus type 1 preferentially targets human colon carcinoma: role of extracellular matrix. J Virol 82:999–1010 [View Article][PubMed]
     [Google Scholar]
  31. Li J., Hu S., Zhou L., Ye L., Wang X., Ho J., Ho W. 2011; Interferon lambda inhibits herpes simplex virus type I infection of human astrocytes and neurons. Glia 59:58–67 [View Article][PubMed]
     [Google Scholar]
  32. Liu J., Thorp S. C. 2002; Cell surface heparan sulfate and its roles in assisting viral infections. Med Res Rev 22:1–25 [View Article][PubMed]
     [Google Scholar]
  33. Margolis R. U., Margolis R. K., Chang L. B., Preti C. 1975; Glycosaminoglycans of brain during development. Biochemistry 14:85–88 [View Article][PubMed]
     [Google Scholar]
  34. Molnar M. J., Gilbert R., Lu Y., Liu A. B., Guo A., Larochelle N., Orlopp K., Lochmuller H., Petrof B. J., Nalbantoglu J. 2004; Factors influencing the efficacy, longevity, and safety of electroporation-assisted plasmid-based gene transfer into mouse muscles. Mol Ther 10:447–455 [View Article][PubMed]
     [Google Scholar]
  35. Mozdziak P., Schultz E. 2000; Retroviral labeling is an appropriate marker for dividing cells. Biotech Histochem 75:141–146 [View Article][PubMed]
     [Google Scholar]
  36. Naldini L., Blömer U., Gallay P., Ory D., Mulligan R., Gage F. H., Verma I. M., Trono D. 1996; In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272:263–267 [View Article][PubMed]
     [Google Scholar]
  37. Namba T., Mochizuki H., Onodera M., Mizuno Y., Namiki H., Seki T. 2005; The fate of neural progenitor cells expressing astrocytic and radial glial markers in the postnatal rat dentate gyrus. Eur J Neurosci 22:1928–1941 [View Article][PubMed]
     [Google Scholar]
  38. Norgren R. B. Jr, Lehman M. N. 1998; Herpes simplex virus as a transneuronal tracer. Neurosci Biobehav Rev 22:695–708 [View Article][PubMed]
     [Google Scholar]
  39. Novak U., Kaye A. H. 2000; Extracellular matrix and the brain: components and function. J Clin Neurosci 7:280–290 [View Article][PubMed]
     [Google Scholar]
  40. Roizman B., Knipe D. M., Whitley R. J. 2007; Herpes simplex viruses. In Fields Virology, 5th edn. pp. 2502–2601 Edited by Knipe D. M. Philadelphia: Lippincott Williams & Wilkins;
     [Google Scholar]
  41. Schmid R. S., Anton E. S. 2003; Role of integrins in the development of the cerebral cortex. Cereb Cortex 13:219–224 [View Article][PubMed]
     [Google Scholar]
  42. Spear P. G. 2004; Herpes simplex virus: receptors and ligands for cell entry. Cell Microbiol 6:401–410 [View Article][PubMed]
     [Google Scholar]
  43. Steiner I. 2003; Herpes simplex viruses. In Clinical Neurovirology pp. 109–129 Edited by Berger A. N. J. R. NewYork: MarcelDekker; [View Article]
     [Google Scholar]
  44. Stoppini L., Buchs P. A., Muller D. 1991; A simple method for organotypic cultures of nervous tissue. J Neurosci Methods 37:173–182 [View Article][PubMed]
     [Google Scholar]
  45. Taylor S. W., Smith R. M., Pari G., Wobeser W., Rossiter J. P., Jackson A. C. 2005; Herpes simplex encephalitis. Can J Neurol Sci 32:246–247[PubMed] [CrossRef]
     [Google Scholar]
  46. Thomas S. K., Gough G., Latchman D. S., Coffin R. S. 1999; Herpes simplex virus latency-associated transcript encodes a protein which greatly enhances virus growth, can compensate for deficiencies in immediate-early gene expression, and is likely to function during reactivation from virus latency. J Virol 73:6618–6625[PubMed]
     [Google Scholar]
  47. Thomas H. C., Kapadia R. D., Wells G. I., Gresham A. M., Sutton D., Solleveld H. A., Sarkar S. K., Dillon S. B., Tal-Singer R. 2001; Differences in pathogenicity of herpes simplex virus serotypes 1 and 2 may be observed by histopathology and high-resolution magnetic resonance imaging in a murine encephalitis model. J Neurovirol 7:105–116 [View Article][PubMed]
     [Google Scholar]
  48. van Praag H., Schinder A. F., Christie B. R., Toni N., Palmer T. D., Gage F. H. 2002; Functional neurogenesis in the adult hippocampus. Nature 415:1030–1034 [View Article][PubMed]
     [Google Scholar]
  49. Wu H., Seki T., Dmitriev I., Uil T., Kashentseva E., Han T., Curiel D. T. 2002; Double modification of adenovirus fiber with RGD and polylysine motifs improves coxsackievirus-adenovirus receptor-independent gene transfer efficiency. Hum Gene Ther 13:1647–1653 [View Article][PubMed]
     [Google Scholar]
  50. Wuest T. R., Carr D. J. 2008; The role of chemokines during herpes simplex virus-1 infection. Front Biosci 13:4862–4872 [View Article][PubMed]
     [Google Scholar]
  51. Ybot-Gonzalez P., Copp A. J., Greene N. D. 2005; Expression pattern of glypican-4 suggests multiple roles during mouse development. Dev Dyn 233:1013–1017 [View Article][PubMed]
     [Google Scholar]
  52. Yura Y., Iga H., Kondo Y., Harada K., Tsujimoto H., Yanagawa T., Yoshida H., Sato M. 1992; Heparan sulfate as a mediator of herpes simplex virus binding to basement membrane. J Invest Dermatol 98:494–498 [View Article][PubMed]
     [Google Scholar]
/content/journal/jgv/10.1099/vir.0.031013-0
Loading
Restrictions that control herpes simplex virus type 1 infection in mouse brain ex vivo
J. Gen. Virol. 92, 2383 (2011); https://doi.org/10.1099/vir.0.031013-0
/content/journal/jgv/10.1099/vir.0.031013-0
/content/journal/jgv/10.1099/vir.0.031013-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Most cited 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