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Journal of Virology, November 2009, p. 11607-11615, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.01369-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Insertional Mutations in Herpes Simplex Virus Type 1 gL Identify Functional Domains for Association with gH and for Membrane Fusion{triangledown}

Qing Fan,{dagger} Erick Lin,{dagger},{ddagger} and Patricia G. Spear*

Department of Microbiology-Immunology, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611

Received 3 July 2009/ Accepted 25 August 2009

Glycoprotein L (gL) is one of four glycoproteins required for the entry of herpes simplex virus (HSV) into cells and for virus-induced cell fusion. This glycoprotein oligomerizes with gH to form a membrane-bound heterodimer but can be secreted when expressed without gH. Twelve unique gL linker-insertion mutants were generated to identify regions critical for gH binding and gH/gL processing and regions essential for cell fusion and viral entry. All gL mutants were detected on the cell surface in the absence of gH, suggesting incomplete cleavage of the signal peptide or the presence of a cell surface receptor for secreted gL. Coexpression with gH enhanced the levels of cell surface gL detected by antibodies for all gL mutants except those that were defective in their interactions with gH. Two insertions into a conserved region of gL abrogated the binding of gL to gH and prevented gH expression on the cell surface. Three other insertions reduced the cell surface expression of gH and/or altered the properties of gH/gL heterodimers. Altered or absent interaction of gL with gH was correlated with reduced or absent cell fusion activity and impaired complementation of virion infectivity. These results identify a conserved domain of gL that is critical for its binding to gH and two noncontiguous regions of gL, one of which contains the conserved domain, that are critical for the gH/gL complex to perform its role in membrane fusion.

* Corresponding author. Mailing address: Northwestern University, Department of Microbiology-Immunology, Mail Code S213, 320 East Superior Street, Chicago, IL 60611. Phone: (312) 503-8230. Fax: (312) 503-1339. E-mail: p-spear{at}northwestern.edu

{triangledown} Published ahead of print on 2 September 2009.

{dagger} Q.F. and E.L. contributed equally to this work.

{ddagger} Present address: Department of Pathology, UCLA Medical Center, Los Angeles, CA.

Journal of Virology, November 2009, p. 11607-11615, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.01369-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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