Herpes simplex virus with highly reduced gD levels can efficiently enter and spread between human keratinocytes

Citation
Mt. Huber et al., Herpes simplex virus with highly reduced gD levels can efficiently enter and spread between human keratinocytes, J VIROLOGY, 75(21), 2001, pp. 10309-10318
Citations number
33
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Microbiology
Journal title
JOURNAL OF VIROLOGY
ISSN journal
0022-538X → ACNP
Volume
75
Issue
21
Year of publication
2001
Pages
10309 - 10318
Database
ISI
SICI code
0022-538X(200111)75:21<10309:HSVWHR>2.0.ZU;2-1
Abstract
The rapid spread of herpes simplex virus type 1 (HSV-1) in mucosal epitheli a and neuronal tissue depends primarily on the ability of the virus to navi gate within polarized cells and the tissues they constitute. To understand HSV entry and the spread of virus across cell junctions, we have previously characterized a human keratinocyte cell line, HaCaT. These cells appear to reflect cells infected in vivo more accurately than many of the cultured c ells used to propagate HSV. HSV mutants lacking gE/gI are highly compromise d in spread within epithelial and neuronal tissues and also show defects in cell-to-cell spread in HaCaT cells, but not in other, nonpolarized cells. HSV gD is normally considered absolutely essential for entry and cell-to-ce ll spread, both in cultured cells and in vivo. Here, an HSV-1 gD mutant vir us, F-US6kan, was found to efficiently enter HaCaT cells and normal human k eratinocytes and could spread from cell to cell without gD provided by comp lementing cells. By contrast, entry and spread into other cells, especially highly transformed cells commonly used to propagate HSV, were extremely in efficient. Further analyses of F-US6kan indicated that this mutant expresse d extraordinarily low (1/500 wild-type) levels of gD. Neutralizing anti-gD monoclonal antibodies inhibited entry of F-US6kan, suggesting F-US6kan util ized this small amount of gD to enter cells. HaCaT cells expressed high lev els of an HSV gD receptor, HveC, and entry of F-US6kan into HaCaT cells cou ld also be inhibited with antibodies specific for HveC. Interestingly, anti -HveC antibodies were not fully able to inhibit entry of wild-type HSV-1 in to HaCaT cells. These results help to uncover important properties of HSV a nd human keratinocytes. HSV, with exceedingly low levels of a crucial recep tor-binding glycoprotein, can enter cells expressing high levels of recepto r. In this case, surplus gD may be useful to avoid neutralization by anti-g D antibodies.