Infection of neurons and encephalitis after intracranial inoculation of herpes simplex virus requires the entry receptor nectin-1

Kopp, S. J., Banisadr, G., Glajch, K., Maurer, U. E., Grunewald, K., Miller, R. J., Osten, P., Spear, P. G. (2009) Infection of neurons and encephalitis after intracranial inoculation of herpes simplex virus requires the entry receptor nectin-1. Proceedings of the National Academy of Sciences of the United States of America, 106 (42). pp. 17916-20. ISSN 0027-8424

URL: http://www.ncbi.nlm.nih.gov/pubmed/19805039
DOI: 10.1073/pnas.0908892106

Abstract

Multiple entry receptors can mediate infection of cells by herpes simplex virus (HSV), permitting alternative pathways for infection and disease. We investigated the roles of two known entry receptors, herpesvirus entry mediator (HVEM) and nectin-1, in infection of neurons in the CNS and the development of encephalitis. Wild-type, HVEM KO, nectin-1 KO, and HVEM/nectin-1 double KO mice were inoculated with HSV into the hippocampus. The mice were examined for development of encephalitis or were killed at various times after inoculation for immunohistological analyses of brain slices. Nectin-1 KO mice showed no signs of disease after intracranial inoculation, and no HSV antigens were detectable in the brain parenchyma. However, HSV antigens were detected in non-parenchymal cells lining the ventricles. In the double KO mice, there was also no disease and no detectable expression of viral antigens even in non-parenchymal cells, indicating that infection of these cells in the nectin-1 KO mice was dependent on the expression of HVEM. Wild-type and HVEM KO mice rapidly developed encephalitis, and the patterns of HSV replication in the brain were indistinguishable. Thus, expression of nectin-1 is necessary for HSV infection via the intracranial route and for encephalitis; HVEM is largely irrelevant. These results contrast with recent findings that (i) either HVEM or nectin-1 can permit HSV infection of the vaginal epithelium in mice and (ii) nectin-1 is not the sole receptor capable of enabling spread of HSV infection from the vaginal epithelium to the PNS and CNS.

Item Type: Paper
Uncontrolled Keywords: HSV pathogenesis
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types

organs, tissues, organelles, cell types and functions > cell types and functions
organism description > virus > herpes simplex virus
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons

organs, tissues, organelles, cell types and functions
organism description > virus
CSHL Authors:
Communities: CSHL labs > Osten lab
Depositing User: Matt Covey
Date Deposited: 20 Feb 2013 21:25
Last Modified: 05 Apr 2013 16:41
PMCID: PMC2764878
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27396

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