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Journal of Virology, December 2000, p. 11437-11446, Vol. 74, No. 24
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Mutations in Herpes Simplex Virus Glycoprotein D Distinguish Entry of Free Virus from Cell-Cell Spread

Daniel A. Rauch, Nilda Rodriguez, and Richard J. Roller*

Department of Microbiology, University of Iowa, Iowa City, Iowa 52242

Received 13 June 2000/Accepted 18 September 2000

Herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) is an essential component of the entry apparatus that is responsible for viral penetration and subsequent cell-cell spread. To test the hypothesis that gD may serve distinguishable functions in entry of free virus and cell-cell spread, mutants were selected for growth on US11cl19.3 cells, which are resistant to both processes due to the lack of a functional gD receptor, and then tested for their ability to enter as free virus and to spread from cell to cell. Unlike their wild-type parent, HSV-1(F), the variants that emerged from this selection, which were named SP mutants, are all capable of forming macroscopic plaques on the resistant cells. This ability is caused by a marked increase in cell-cell spread without a concomitant increase in efficiency of entry of free virus. gD substitutions that arose within these mutants are sufficient to mediate cell-cell spread in US11cl19.3 cells but are insufficient to overcome the restriction to entry of free virions. These results suggest that mutations in gD (i) are sufficient but not necessary to overcome the block to cell-cell spread exhibited by US11cl19.3 cells and (ii) are insufficient to mediate entry of free virus in the same cells.

* Corresponding author. Mailing address: Department of Microbiology, The University of Iowa, 3-752 Bowen Science Building, Iowa City, IA 52242. Phone: (319) 335-9958. Fax: (319) 335-9006. E-mail: richard-roller{at}uiowa.edu.

Journal of Virology, December 2000, p. 11437-11446, Vol. 74, No. 24
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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