ICP47 mediates viral neuroinvasiveness by induction of TAP protein following intravenous inoculation of herpes simplex virus type 1 in mice

被引:13
作者
Burgos, Javier S. [1 ]
Serrano-Saiz, Esther
Sastre, Isabel
Valdivieso, Fernando
机构
[1] Univ Autonoma Madrid, Lab CX340, Ctr Biol Mol Severo Ochoa, CSIC, E-28049 Madrid, Spain
[2] Univ Autonoma Madrid, Dept Biol Mol, E-28049 Madrid, Spain
关键词
brain; herpes simplex virus type 1; ICP47; mice; TAP;
D O I
10.1080/13550280601009546
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:420 / 427
页数:8
相关论文
共 38 条
[31]   PEPTIDE LENGTH AND SEQUENCE SPECIFICITY OF THE MOUSE TAP1/TAP2 TRANSLOCATOR [J].
SCHUMACHER, TNM ;
KANTESARIA, DV ;
HEEMELS, MT ;
ASHTONRICKARDT, PG ;
SHEPHERD, JC ;
FRUH, K ;
YANG, Y ;
PETERSON, PA ;
TONEGAWA, S ;
PLOEGH, HL .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 179 (02) :533-540
[32]   A GENE IN THE HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II REGION CONTROLLING THE CLASS-I ANTIGEN PRESENTATION PATHWAY [J].
SPIES, T ;
BRESNAHAN, M ;
BAHRAM, S ;
ARNOLD, D ;
BLANCK, G ;
MELLINS, E ;
PIOUS, D ;
DEMARS, R .
NATURE, 1990, 348 (6303) :744-747
[33]   HERPES-SIMPLEX VIRUS LATENT INFECTION IN THE NERVOUS-SYSTEM [J].
STEINER, I ;
KENNEDY, PGE .
JOURNAL OF NEUROVIROLOGY, 1995, 1 (01) :19-29
[34]   Stable binding of the herpes simplex virus ICP47 protein to the peptide binding site of TAP [J].
Tomazin, R ;
Hill, AB ;
Jugovic, P ;
York, I ;
vanEndert, P ;
Ploegh, HL ;
Andrews, DW ;
Johnson, DC .
EMBO JOURNAL, 1996, 15 (13) :3256-3266
[35]   ELECTROPHORETIC TRANSFER OF PROTEINS FROM POLYACRYLAMIDE GELS TO NITROCELLULOSE SHEETS - PROCEDURE AND SOME APPLICATIONS [J].
TOWBIN, H ;
STAEHELIN, T ;
GORDON, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1979, 76 (09) :4350-4354
[36]  
TOWNSEND A, 1989, ANNU REV IMMUNOL, V7, P601, DOI 10.1146/annurev.immunol.7.1.601
[37]  
VANKAER L, 1992, CELL, V71, P1205, DOI 10.1016/S0092-8674(05)80068-6
[38]   A CYTOSOLIC HERPES-SIMPLEX VIRUS PROTEIN INHIBITS ANTIGEN PRESENTATION TO CD8(+) T-LYMPHOCYTES [J].
YORK, IA ;
ROOP, C ;
ANDREWS, DW ;
RIDDELL, SR ;
GRAHAM, FL ;
JOHNSON, DC .
CELL, 1994, 77 (04) :525-535