Herpes simplex virus type 2 ICP47 inhibits human TAP but not mouse TAP.
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 K(D) for ICP47-2 binding to human TAP was 4.8 x 10(-8) M, virtually identical to that measured for ICP47-1 (5.2 x 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.
Tomazin
R
R
Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland 97201, USA.
van Schoot
N E
NE
Goldsmith
K
K
Jugovic
P
P
Sempé
P
P
Früh
K
K
Johnson
D C
DC
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D008285:Major Histocompatibility Complex; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000235:genetics; D018411:Spodoptera / Q000166:cytology; D014764:Viral Proteins
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; C105843:ICP47 protein, Herpes simplex virus; D017874:Immediate-Early Proteins; D011993:Recombinant Fusion Proteins; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; C489516:Tap2 protein, mouse; D014764:Viral Proteins; C071692:TAP2 protein, human