HERPES-SIMPLEX VIRUS TYPE-2 ICP47 INHIBITS HUMAN TAP BUT NOT MOUSE TAP

Herpes simplex virus serotype 1 (HSV-1) expresses an immediate-early p rotein, ICP47, that effectively blocks the major histocompatibility co mplex class I antigen presentation pathway. HSV-1 ICP47 (ICP47-1) bind s with high affinity to the human transporter associated with antigen presentation (TAP) and blocks the binding of antigenic peptides, HSV t ype 2 (HSV-2) ICP47 (ICP47-2) has only 42% amino acid sequence identit y with ICP47-1, Here, He compared the levels of inhibition of human an d murine TAP expressed in insect cell microsomes, by ICP47-1 and ICP47 -2, Both proteins inhibited human TAP at similar concentrations, and t he li,for ICP47-2 binding to human TAP was 4.8 x 10(-8) hi, virtually identical to that measured for ICP47-1 (5.2 x 10(-8) M), There was som e inhibition of murine TAP by both ICP47-2 and ICP47-1, but this inhib ition was incomplete and only at ICP47 concentrations 50 to 100 times that required to inhibit human TAP. Lack of inhibition of murine TAP b y ICP47-1 and ICP47-2 could be explained by an inability of both prote ins to bind to murine TAP.