Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1996 Aug;70(8):5405–5413. doi: 10.1128/jvi.70.8.5405-5413.1996

Anterograde, transneuronal transport of herpes simplex virus type 1 strain H129 in the murine visual system.

N Sun 1, M D Cassell 1, S Perlman 1
PMCID: PMC190498  PMID: 8764051

Abstract

Herpes simplex virus (HSV) undergoes retrograde and anterograde axonal transport as it establishes latency and later intermittently reactivates. Most strains of HSV show preferential retrograde transport within the central nervous system (CNS), however. Previous experiments suggest that an exception to this is HSV type 1 (HSV-1) strain H129, since this virus appears to spread primarily in the CNS via anterograde, transneuronal movement. The objective of the present study was to test how specifically this virus spreads in the visual system, a system with well-described neuronal connections. In the present study, the pattern of viral spread was examined following inoculation into the murine vitreous body. Virus was initially detected in the retina and optic tract. Virus then appeared in all known primary targets of the retina, including those in the thalamus (e.g., lateral geniculate complex), hypothalamus (suprachiasmatic nucleus), and superior colliculus (superficial layers). In previous studies, many strains of HSV were shown to infect these structures, even though they spread predominantly in a retrograde direction. However, the H129 strain was unique in then spreading, via anterograde transport, to the primary visual cortex (layer 4 of area 17) via thalamocortical connections. At later times after infection, specific labeling was also detected in other cortical and subcortical areas known to receive projections from the visual cortex. No labeling was ever detected in the contralateral retina, which is consistent with a lack of retrograde spread of HSV-1 strain H129. These results demonstrate the specific anterograde movement of this virus from the retina to subcortical and cortical regions, with no clear evidence for retrograde spread. HSV-1 strain H129 should be generally useful for tracing sensory pathways and may provide the basis for designing a virus vector capable of delivering genetic material via anterograde pathways within the CNS.

Full Text

The Full Text of this article is available as a PDF (1.9 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Balan P., Davis-Poynter N., Bell S., Atkinson H., Browne H., Minson T. An analysis of the in vitro and in vivo phenotypes of mutants of herpes simplex virus type 1 lacking glycoproteins gG, gE, gI or the putative gJ. J Gen Virol. 1994 Jun;75(Pt 6):1245–1258. doi: 10.1099/0022-1317-75-6-1245. [DOI] [PubMed] [Google Scholar]
  2. Barnett E. M., Cassell M. D., Perlman S. Two neurotropic viruses, herpes simplex virus type 1 and mouse hepatitis virus, spread along different neural pathways from the main olfactory bulb. Neuroscience. 1993 Dec;57(4):1007–1025. doi: 10.1016/0306-4522(93)90045-H. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barnett E. M., Evans G. D., Sun N., Perlman S., Cassell M. D. Anterograde tracing of trigeminal afferent pathways from the murine tooth pulp to cortex using herpes simplex virus type 1. J Neurosci. 1995 Apr;15(4):2972–2984. doi: 10.1523/JNEUROSCI.15-04-02972.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barnett E. M., Jacobsen G., Evans G., Cassell M., Perlman S. Herpes simplex encephalitis in the temporal cortex and limbic system after trigeminal nerve inoculation. J Infect Dis. 1994 Apr;169(4):782–786. doi: 10.1093/infdis/169.4.782. [DOI] [PubMed] [Google Scholar]
  5. Blessing W. W., Ding Z. Q., Li Y. W., Gieroba Z. J., Wilson A. J., Hallsworth P. G., Wesselingh S. L. Transneuronal labelling of CNS neurons with herpes simplex virus. Prog Neurobiol. 1994 Sep;44(1):37–53. doi: 10.1016/0301-0082(94)90056-6. [DOI] [PubMed] [Google Scholar]
  6. Card J. P., Rinaman L., Schwaber J. S., Miselis R. R., Whealy M. E., Robbins A. K., Enquist L. W. Neurotropic properties of pseudorabies virus: uptake and transneuronal passage in the rat central nervous system. J Neurosci. 1990 Jun;10(6):1974–1994. doi: 10.1523/JNEUROSCI.10-06-01974.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Card J. P., Whealy M. E., Robbins A. K., Moore R. Y., Enquist L. W. Two alpha-herpesvirus strains are transported differentially in the rodent visual system. Neuron. 1991 Jun;6(6):957–969. doi: 10.1016/0896-6273(91)90236-s. [DOI] [PubMed] [Google Scholar]
  8. Cassone V. M., Speh J. C., Card J. P., Moore R. Y. Comparative anatomy of the mammalian hypothalamic suprachiasmatic nucleus. J Biol Rhythms. 1988 Spring;3(1):71–91. doi: 10.1177/074873048800300106. [DOI] [PubMed] [Google Scholar]
  9. Caviness V. S., Jr, Frost D. O. Thalamocortical projections in the reeler mutant mouse. J Comp Neurol. 1983 Sep 10;219(2):182–202. doi: 10.1002/cne.902190205. [DOI] [PubMed] [Google Scholar]
  10. Dingwell K. S., Doering L. C., Johnson D. C. Glycoproteins E and I facilitate neuron-to-neuron spread of herpes simplex virus. J Virol. 1995 Nov;69(11):7087–7098. doi: 10.1128/jvi.69.11.7087-7098.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Faull R. L., Nauta W. J., Domesick V. B. The visual cortico-striato-nigral pathway in the rat. Neuroscience. 1986 Dec;19(4):1119–1132. doi: 10.1016/0306-4522(86)90128-4. [DOI] [PubMed] [Google Scholar]
  12. Herkenham M. Laminar organization of thalamic projections to the rat neocortex. Science. 1980 Feb 1;207(4430):532–535. doi: 10.1126/science.7352263. [DOI] [PubMed] [Google Scholar]
  13. Hoover J. E., Strick P. L. Multiple output channels in the basal ganglia. Science. 1993 Feb 5;259(5096):819–821. doi: 10.1126/science.7679223. [DOI] [PubMed] [Google Scholar]
  14. Hughes H. C. Anatomical and neurobehavioral investigations concerning the thalamo-cortical organization of the rat's visual system. J Comp Neurol. 1977 Oct 1;175(3):311–336. doi: 10.1002/cne.901750306. [DOI] [PubMed] [Google Scholar]
  15. Johnson R. F., Morin L. P., Moore R. Y. Retinohypothalamic projections in the hamster and rat demonstrated using cholera toxin. Brain Res. 1988 Oct 18;462(2):301–312. doi: 10.1016/0006-8993(88)90558-6. [DOI] [PubMed] [Google Scholar]
  16. Kristensson K., Ghetti B., Wiśniewski H. M. Study on the propagation of Herpes simplex virus (type 2) into the brain after intraocular injection. Brain Res. 1974 Apr 5;69(2):189–201. doi: 10.1016/0006-8993(74)90001-8. [DOI] [PubMed] [Google Scholar]
  17. Kucera P., Dolivo M., Coulon P., Flamand A. Pathways of the early propagation of virulent and avirulent rabies strains from the eye to the brain. J Virol. 1985 Jul;55(1):158–162. doi: 10.1128/jvi.55.1.158-162.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kuypers H. G., Ugolini G. Viruses as transneuronal tracers. Trends Neurosci. 1990 Feb;13(2):71–75. doi: 10.1016/0166-2236(90)90071-h. [DOI] [PubMed] [Google Scholar]
  19. Lavi E., Fishman P. S., Highkin M. K., Weiss S. R. Limbic encephalitis after inhalation of a murine coronavirus. Lab Invest. 1988 Jan;58(1):31–36. [PubMed] [Google Scholar]
  20. McLean J. H., Shipley M. T., Bernstein D. I. Golgi-like, transneuronal retrograde labelling with CNS injections of herpes simplex virus type 1. Brain Res Bull. 1989 May;22(5):867–881. doi: 10.1016/0361-9230(89)90032-4. [DOI] [PubMed] [Google Scholar]
  21. Miller M. W., Vogt B. A. Direct connections of rat visual cortex with sensory, motor, and association cortices. J Comp Neurol. 1984 Jun 20;226(2):184–202. doi: 10.1002/cne.902260204. [DOI] [PubMed] [Google Scholar]
  22. Millhouse O. E. Optic chiasm collaterals afferent to the suprachiasmatic nucleus. Brain Res. 1977 Dec 2;137(2):351–355. doi: 10.1016/0006-8993(77)90345-6. [DOI] [PubMed] [Google Scholar]
  23. Moore R. Y., Speh J. C., Card J. P. The retinohypothalamic tract originates from a distinct subset of retinal ganglion cells. J Comp Neurol. 1995 Feb 13;352(3):351–366. doi: 10.1002/cne.903520304. [DOI] [PubMed] [Google Scholar]
  24. Nagata T., Hayashi Y. The visual field representation of the rat ventral lateral geniculate nucleus. J Comp Neurol. 1984 Aug 20;227(4):582–588. doi: 10.1002/cne.902270409. [DOI] [PubMed] [Google Scholar]
  25. Norgren R. B., Jr, Lehman M. N. Retrograde transneuronal transport of herpes simplex virus in the retina after injection in the superior colliculus, hypothalamus and optic chiasm. Brain Res. 1989 Feb 13;479(2):374–378. doi: 10.1016/0006-8993(89)91644-2. [DOI] [PubMed] [Google Scholar]
  26. Norgren R. B., Jr, McLean J. H., Bubel H. C., Wander A., Bernstein D. I., Lehman M. N. Anterograde transport of HSV-1 and HSV-2 in the visual system. Brain Res Bull. 1992 Mar;28(3):393–399. doi: 10.1016/0361-9230(92)90038-y. [DOI] [PubMed] [Google Scholar]
  27. Shipley M. T., Geinisman Y. Anatomical evidence for convergence of olfactory, gustatory, and visceral afferent pathways in mouse cerebral cortex. Brain Res Bull. 1984 Mar;12(3):221–226. doi: 10.1016/0361-9230(84)90049-2. [DOI] [PubMed] [Google Scholar]
  28. Simmons P. A., Lemmon V., Pearlman A. L. Afferent and efferent connections of the striate and extrastriate visual cortex of the normal and reeler mouse. J Comp Neurol. 1982 Nov 1;211(3):295–308. doi: 10.1002/cne.902110308. [DOI] [PubMed] [Google Scholar]
  29. Stein B. E. Organization of the rodent superior colliculus: some comparisons with other mammals. Behav Brain Res. 1981 Sep;3(2):175–188. doi: 10.1016/0166-4328(81)90046-2. [DOI] [PubMed] [Google Scholar]
  30. Sun N., Grzybicki D., Castro R. F., Murphy S., Perlman S. Activation of astrocytes in the spinal cord of mice chronically infected with a neurotropic coronavirus. Virology. 1995 Nov 10;213(2):482–493. doi: 10.1006/viro.1995.0021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Thompson S. M., Robertson R. T. Organization of subcortical pathways for sensory projections to the limbic cortex. II. Afferent projections to the thalamic lateral dorsal nucleus in the rat. J Comp Neurol. 1987 Nov 8;265(2):189–202. doi: 10.1002/cne.902650204. [DOI] [PubMed] [Google Scholar]
  32. Ugolini G., Kuypers H. G., Strick P. L. Transneuronal transfer of herpes virus from peripheral nerves to cortex and brainstem. Science. 1989 Jan 6;243(4887):89–91. doi: 10.1126/science.2536188. [DOI] [PubMed] [Google Scholar]
  33. Ugolini G. Transneuronal transfer of herpes simplex virus type 1 (HSV 1) from mixed limb nerves to the CNS. I. Sequence of transfer from sensory, motor, and sympathetic nerve fibres to the spinal cord. J Comp Neurol. 1992 Dec 22;326(4):527–548. doi: 10.1002/cne.903260404. [DOI] [PubMed] [Google Scholar]
  34. Vann V. R., Atherton S. S. Neural spread of herpes simplex virus after anterior chamber inoculation. Invest Ophthalmol Vis Sci. 1991 Aug;32(9):2462–2472. [PubMed] [Google Scholar]
  35. Vrang N., Larsen P. J., Møller M., Mikkelsen J. D. Topographical organization of the rat suprachiasmatic-paraventricular projection. J Comp Neurol. 1995 Mar 20;353(4):585–603. doi: 10.1002/cne.903530409. [DOI] [PubMed] [Google Scholar]
  36. Watts A. G., Swanson L. W., Sanchez-Watts G. Efferent projections of the suprachiasmatic nucleus: I. Studies using anterograde transport of Phaseolus vulgaris leucoagglutinin in the rat. J Comp Neurol. 1987 Apr 8;258(2):204–229. doi: 10.1002/cne.902580204. [DOI] [PubMed] [Google Scholar]
  37. Wenisch H. J. Retinohypothalamic projection in the mouse: electron microscopic and iontophoretic investigations of hypothalamic and optic centers. Cell Tissue Res. 1976 Apr 9;167(4):547–561. doi: 10.1007/BF00215184. [DOI] [PubMed] [Google Scholar]
  38. Whealy M. E., Card J. P., Robbins A. K., Dubin J. R., Rziha H. J., Enquist L. W. Specific pseudorabies virus infection of the rat visual system requires both gI and gp63 glycoproteins. J Virol. 1993 Jul;67(7):3786–3797. doi: 10.1128/jvi.67.7.3786-3797.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Whitley R. J. Viral encephalitis. N Engl J Med. 1990 Jul 26;323(4):242–250. doi: 10.1056/NEJM199007263230406. [DOI] [PubMed] [Google Scholar]
  40. Zemanick M. C., Strick P. L., Dix R. D. Direction of transneuronal transport of herpes simplex virus 1 in the primate motor system is strain-dependent. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8048–8051. doi: 10.1073/pnas.88.18.8048. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES