ICP47 mediates viral neuroinvasiveness by induction of TAP protein following intravenous inoculation of herpes simplex virus type 1 in mice.
Herpes simplex virus type 1 (HSV-1) expresses an immediate-early protein, ICP47, that blocks the major histocompatibility complex class I antigen presentation pathway by binding to the transporter associated with antigen presentation (TAP). The result is the virus' evasion of the immune system. Although the interaction between ICP47 and TAP has been examined in vitro, this paper is the first to report their interaction in vivo. In C57BL/6 adult female mice, ICP47-defective virus (Delta ICP47, F strain) was less able to invade the organs studied than was wild-type HSV-1 F strain, showing that ICP47 influences general invasiveness. However, the neuroinvasiveness of the Delta ICP47 virus was recovered in TAP-deficient mice, indicating that the TAP-ICP47 interaction is specific to neural tissues. HSV-1 F strain showed no significant differences in their invasiveness in TAP-deficient and wild-type mice. Therefore, although ICP47 appears to be essential for invasion, the presence of TAP appears not to be crucial. Western blotting showed TAP1 expression to increase by at least fourfold in the brains and adrenal glands of infected mice. This suggests that TAP plays an important role in the host defense system. This increased expression may be particularly important in the encephalon since the baseline protein levels of this organ are low (ratio adrenal protein level/encephalon protein level > 100). However, Delta ICP47 virus provoked no significant increase in the brain TAP1 levels of wild-type mice because it could not invade this organ. These results suggest that ICP47 plays a role in infection, and that TAP1 production is regulated during viral challenge.
Burgos
Javier S
JS
Departamento de Biología Molecular and Centro de Biologí Molecular Severo Ochoa, C.S.I.C.-U.A.M., Universidad Autónoma de Madrid, Madrid, Spain. jburgos@cbm.uam.es
Serrano-Saiz
Esther
E
Sastre
Isabel
I
Valdivieso
Fernando
F
D000818:Animals; D000950:Antigens, Ly / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000821:virology*; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology / Q000472:pathogenicity*; D017874:Immediate-Early Proteins / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism*
D000950:Antigens, Ly; C105843:ICP47 protein, Herpes simplex virus; D017874:Immediate-Early Proteins; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D014764:Viral Proteins