Herpes simplex virus glycoproteins E and I facilitate cell-to-cell spread in vivo and across junctions of cultured cells

Kevin S. Dingwell, Craig R. Brunetti, Robert L. Hendricks, Qizhi Tang, Mary Tang, Andrew J. Rainbow, David Johnson

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Abstract

Herpes simplex virus (HSV) glycoproteins E and I (gE and gI) can act as a receptor for the Fc domain of immunoglobulin G (IgG). To examine the role of HSV IgG Fc receptor in viral pathogenesis, rabbits and mice were infected by the corneal route with HSV gE- or gI- mutants. Wild-type HSV-1 produced large dendritic lesions in the corneal epithelium and subsequent stromal disease leading to viral encephalitis, whereas gE- and gI- mutant viruses produced microscopic punctate or small dendritic lesions in the epithelium and no corneal disease or encephalitis. These differences were not related to the ability of the gE-gI oligomer to bind IgG because the differences were observed before the appearance of anti-HSV IgG and in mice, in which IgG binds to the Fc receptor poorly or not at all. Mutant viruses produced small plaques on monolayers of normal human fibroblasts and epithelial cells. Replication of gE- and gI- mutant viruses in human fibroblasts were normal, and the rates of entry of mutant and wild-type viruses into fibroblasts were similar; however, spread of gE- and gI- mutant viruses from cell to cell was significantly slower than that of wild-type HSV-1. In experiments in which fibroblast monolayers were infected with low multiplicities of virus and multiple rounds of infection occurred, the presence of neutralizing antibodies in the culture medium caused the yields of mutant viruses to drop dramatically, whereas there was a lesser effect on the production of wild- type HSV. It appears that cell-to-cell transmission of wild-type HSV-1 occurs by at least two mechanisms: (i) release of virus from cells and entry of extracellular virus into a neighboring cell and (ii) transfer of virus across cell junctions in a manner resistant to neutralizing antibodies. Our results suggest that gE- and gI- mutants are defective in the latter mechanism of spread, suggesting the possibility that the gE-gI complex facilitates virus transfer across cell junctions, a mode of spread which may predominate in some tissues. It is ironic that the gE-gI complex, usually considered an IgG Fc receptor, may, through its ability to mediate cell-to-cell spread, actually protect HSV from IgG in a manner different than previously thought.

Original languageEnglish (US)
Pages (from-to)834-845
Number of pages12
JournalJournal of Virology
Volume68
Issue number2
StatePublished - Feb 1994
Externally publishedYes

Fingerprint

herpes simplex
Simplexvirus
cultured cells
glycoproteins
Cultured Cells
Glycoproteins
Viruses
viruses
immunoglobulin G
Immunoglobulin G
cells
Fc Receptors
Human Herpesvirus 1
mutants
Fibroblasts
IgG Receptors
Human herpesvirus 1
Intercellular Junctions
fibroblasts
Neutralizing Antibodies

ASJC Scopus subject areas

  • Immunology

Cite this

Dingwell, K. S., Brunetti, C. R., Hendricks, R. L., Tang, Q., Tang, M., Rainbow, A. J., & Johnson, D. (1994). Herpes simplex virus glycoproteins E and I facilitate cell-to-cell spread in vivo and across junctions of cultured cells. Journal of Virology, 68(2), 834-845.

Herpes simplex virus glycoproteins E and I facilitate cell-to-cell spread in vivo and across junctions of cultured cells. / Dingwell, Kevin S.; Brunetti, Craig R.; Hendricks, Robert L.; Tang, Qizhi; Tang, Mary; Rainbow, Andrew J.; Johnson, David.

In: Journal of Virology, Vol. 68, No. 2, 02.1994, p. 834-845.

Research output: Contribution to journalArticle

Dingwell, KS, Brunetti, CR, Hendricks, RL, Tang, Q, Tang, M, Rainbow, AJ & Johnson, D 1994, 'Herpes simplex virus glycoproteins E and I facilitate cell-to-cell spread in vivo and across junctions of cultured cells', Journal of Virology, vol. 68, no. 2, pp. 834-845.
Dingwell KS, Brunetti CR, Hendricks RL, Tang Q, Tang M, Rainbow AJ et al. Herpes simplex virus glycoproteins E and I facilitate cell-to-cell spread in vivo and across junctions of cultured cells. Journal of Virology. 1994 Feb;68(2):834-845.
Dingwell, Kevin S. ; Brunetti, Craig R. ; Hendricks, Robert L. ; Tang, Qizhi ; Tang, Mary ; Rainbow, Andrew J. ; Johnson, David. / Herpes simplex virus glycoproteins E and I facilitate cell-to-cell spread in vivo and across junctions of cultured cells. In: Journal of Virology. 1994 ; Vol. 68, No. 2. pp. 834-845.
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