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, He 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 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 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.