scholarly journals Effect of herpes simplex virus types 1 and 2 on surface expression of class I major histocompatibility complex antigens on infected cells.

1985 ◽  
Vol 56 (3) ◽  
pp. 757-766 ◽  
Author(s):  
S R Jennings ◽  
P L Rice ◽  
E D Kloszewski ◽  
R W Anderson ◽  
D L Thompson ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Surface Expression ◽  
Class I ◽  
Major Histocompatibility ◽  
Major Histocompatibility Complex Antigens ◽  
Histocompatibility Complex ◽  
Infected Cells ◽  
Simplex Virus

scholarly journals Inhibition of Major Histocompatibility Complex Class I Antigen Presentation in Pig and Primate Cells by Herpes Simplex Virus Type 1 and 2 ICP47

1998 ◽  
Vol 72 (6) ◽  
pp. 5076-5084 ◽  
Author(s):  
Pieter Jugovic ◽  
Ann M. Hill ◽  
Roman Tomazin ◽  
Hidde Ploegh ◽  
David C. Johnson
Keyword(s):  
Major Histocompatibility Complex ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antigen Presentation ◽  
Mhc Class I ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) express an immediate-early protein, ICP47, that effectively inhibits the human transporter associated with antigen presentation (TAP), blocking major histocompatibility complex (MHC) class I antigen presentation to CD8+ T cells. Previous work indicated that the mouse TAP is relatively resistant to inhibition by the HSV-1 and HSV-2 ICP47 proteins (ICP47-1 and ICP47-2) and that mouse cells infected with HSV-1 are lysed by anti-HSV CD8+ cytotoxic T lymphocytes (CTL). Therefore, mice are apparently not suitable animals in which to study the in vivo effects of ICP47. In order to find an animal model, we introduced ICP47-1 and ICP47-2 into cells from various animal species—mice, rats, guinea pigs, rabbits, dogs, pigs, cows, monkeys, and humans—and measured TAP activity in the cells. Both proteins were unable to inhibit TAP in mouse, rat, guinea pig, and rabbit cells. In contrast, ICP47-1 and ICP47-2 inhibited TAP in pig, dog, cow, and monkey cells, and the TAP in pig and dog fibroblasts was often more sensitive to both proteins than TAP in human fibroblasts. These results were extended by measuring CD8+-T-cell recognition (CTL lysis) of cells from various species. Cells were infected with recombinant HSV-1 constructed to express murine MHC class I proteins so that the cells would be recognized and lysed by well-characterized murine anti-HSV CTL unless antigen presentation was blocked by ICP47. Anti-HSV CD8+ CTL effectively lysed pig and primate cells infected with a recombinant HSV-1 ICP47− mutant but were unable to lyse pig or primate cells infected with a recombinant HSV-1 that expressed ICP47. Therefore, pigs, dogs, and monkeys may be useful animal models in which to test the effects of ICP47 on HSV pathogenesis or the use of ICP47 as a selective immunosuppressive agent.

scholarly journals The Active Site of ICP47, a Herpes Simplex Virus–encoded Inhibitor of the Major Histocompatibility Complex (MHC)-encoded Peptide Transporter Associated with Antigen Processing (TAP), Maps to the NH2-terminal 35 Residues

1997 ◽  
Vol 185 (9) ◽  
pp. 1565-1572 ◽  
Author(s):  
Begoña Galocha ◽  
Ann Hill ◽  
Barbara C. Barnett ◽  
Aidan Dolan ◽  
Alejandra Raimondi ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Antigen Processing ◽  
Peptide Transporter ◽  
Major Histocompatibility ◽  
Early Protein ◽  
Histocompatibility Complex ◽  
Simplex Virus ◽  
Peptide Translocation

The herpes simplex virus (HSV) immediate early protein ICP47 inhibits the transporter associated with antigen processing (TAP)-dependent peptide translocation. As a consequence, empty major histocompatibility complex (MHC) class I molecules are retained in the endoplasmic reticulum and recognition of HSV-infected cells by cytotoxic T lymphocytes is abolished. We chemically synthesized full-length ICP47 (sICP47) and show that sICP47 inhibits TAP-dependent peptide translocation in human cells. Its biological activity is indistinguishable from that of recombinant ICP47 (rICP47). By using synthetic peptides, we mapped the core sequence of ICP47 minimally required for TAP inhibition to residues 2–35. This segment is located within the region of the molecule conserved between ICP47 from HSV-1 and HSV-2. Through alanine scanning substitution we identified three segments within this region that are critical for the ability to inhibit TAP function. The interaction of ICP47 with TAP is unlikely to mimic precisely that of the transported peptides, as deduced from differential labeling of the TAP1 and TAP2 subunits using sICP47 fragments with chemical cross-linkers.

scholarly journals An Important Role for Major Histocompatibility Complex Class I-Restricted T Cells, and a Limited Role for Gamma Interferon, in Protection of Mice against Lethal Herpes Simplex Virus Infection

1999 ◽  
Vol 73 (3) ◽  
pp. 2058-2063 ◽  
Author(s):  
Ai-Xuan Holterman ◽  
Kathleen Rogers ◽  
Kurt Edelmann ◽  
David M. Koelle ◽  
Lawrence Corey ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Mhc Class I ◽  
Gamma Interferon ◽  
Class I ◽  
Histocompatibility Complex ◽  
Ifn Γ ◽  
Simplex Virus

ABSTRACT Herpes simplex virus (HSV) inhibits major histocompatibility complex (MHC) class I expression in infected cells and does so much more efficiently in human cells than in murine cells. Given this difference, if MHC class I-restricted T cells do not play an important role in protection of mice from HSV, an important role for these cells in humans would be unlikely. However, the contribution of MHC class I-restricted T cells to the control of HSV infection in mice remains unclear. Further, the mechanisms by which these cells may act to control infection, particularly in the nervous system, are not well understood, though a role for gamma interferon (IFN-γ) has been proposed. To address the roles of MHC class I and of IFN-γ, C57BL/6 mice deficient in MHC class I expression (β2 microglobulin knockout [β2KO] mice), in IFN-γ expression (IFN-γKO mice), or in both (IFN-γKO/β2KO mice) were infected with HSV by footpad inoculation. β2KO mice were markedly compromised in their ability to control infection, as indicated by increased lethality and higher concentrations of virus in the feet and spinal ganglia. In contrast, IFN-γ appeared to play at most a limited role in viral clearance. The results suggest that MHC class I-restricted T cells play an important role in protection of mice against neuroinvasive HSV infection and do so largely by mechanisms other than the production of IFN-γ.

scholarly journals Major Histocompatibility Complex Class I Allele-specific Cooperative and Competitive Interactions between Immune Evasion Proteins of Cytomegalovirus

2002 ◽  
Vol 196 (6) ◽  
pp. 805-816 ◽  
Author(s):  
Markus Wagner ◽  
Anja Gutermann ◽  
Jürgen Podlech ◽  
Matthias J. Reddehase ◽  
Ulrich H. Koszinowski
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Surface Expression ◽  
Inhibitory Effect ◽  
Class I ◽  
Major Influence ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Allele Specific ◽  
Infected Cells

Cytomegaloviruses (CMVs) deploy a set of genes for interference with antigen presentation in the major histocompatibility complex (MHC) class I pathway. In murine CMV (MCMV), three genes were identified so far: m04/gp34, m06/gp48, and m152/gp40. While their function as immunoevasins was originally defined after their selective expression, this may not necessarily reflect their biological role during infection. The three immunoevasins might act synergistically, but they might also compete for their common substrate, the MHC class I complexes. To approach this question in a systematic manner, we have generated a complete set of mutant viruses with deletions of the three genes in all seven possible combinations. Surface expression of a set of MHC class I molecules specified by haplotypes H-2d (Kd, Dd, and Ld) and H-2b (Kb and Db) was the parameter for evaluation of the interference with class I trafficking. The data show the following: first, there exists no additional MCMV gene of major influence on MHC class I surface expression; second, the strength of the inhibitory effect of immunoevasins shows an allele-specific hierarchy; and third, the immunoevasins act not only synergistically but can, in certain combinations, interact antagonistically. In essence, this work highlights the importance of studying the immunosubversive mechanisms of cytomegaloviruses in the context of gene expression during the viral replicative cycle in infected cells.

Sign in / Sign up

Export Citation Format

Share Document