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J Virol, March 1998, p. 2560-2563, Vol. 72, No. 3
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Herpes Simplex Virus Type 2 ICP47 Inhibits Human TAP but Not Mouse TAP

Roman Tomazin,1 Nico E. G. van Schoot,1 Kim Goldsmith,1 Pieter Jugovic,1,dagger Pascal Sempé,2 Klaus Früh,2 and David C. Johnson1,*

Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, Oregon 97201,1 and The R. W. Johnson Pharmaceutical Research Institute, Scripps Research Institute, La Jolla, California 920372

Received 8 October 1997/Accepted 20 November 1997

Herpes simplex virus serotype 1 (HSV-1) expresses an immediate-early protein, ICP47, that effectively blocks the major histocompatibility complex class I antigen presentation pathway. HSV-1 ICP47 (ICP47-1) binds with high affinity to the human transporter associated with antigen presentation (TAP) and blocks the binding of antigenic peptides. HSV type 2 (HSV-2) ICP47 (ICP47-2) has only 42% amino acid sequence identity with ICP47-1. Here, we compared the levels of inhibition of human and murine TAP, expressed in insect cell microsomes, by ICP47-1 and ICP47-2. Both proteins inhibited human TAP at similar concentrations, and the KD for ICP47-2 binding to human TAP was 4.8 × 10-8 M, virtually identical to that measured for ICP47-1 (5.2 × 10-8 M). There was some inhibition of murine TAP by both ICP47-2 and ICP47-1, but this inhibition was incomplete and only at ICP47 concentrations 50 to 100 times that required to inhibit human TAP. Lack of inhibition of murine TAP by ICP47-1 and ICP47-2 could be explained by an inability of both proteins to bind to murine TAP.

* Corresponding author. Mailing address: L-220, Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, 3181 S. W. Sam Jackson Park Rd., Portland, OR 97201. Phone: (503) 494-0834. Fax: (503) 494-6862. E-mail: johnsoda{at}ohsu.edu.

dagger Present address: Medical Program, University of Toronto, Toronto, Ontario, Canada.




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