Murine cytomegalovirus-induced suppression of antigen-specific cytotoxic T lymphocyte maturation

Ae, Campbell; Js, Slater; Ws, Futch

doi:10.1016/0042-6822(89)90243-2

Cited by 21 publications

(14 citation statements)

References 29 publications

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“…Virus-specific, CD8 ϩ , MHC class I-restricted CTL are protective against cytomegalovirus disease in humans (43,44) and against lethal infection of mice (32,42). We have demonstrated that in vivo, MCMV infection interferes with the priming of MHC class I-restricted CTL precursors (14,48). Although very few class I molecules are necessary for effective antigen presentation, reduced levels within infected cells may set the stage for competition among peptides presented by class I, thereby skewing the repertoire of peptides presented.…”

Section: Discussionmentioning

confidence: 90%

Multiple independent loci within the human cytomegalovirus unique short region down-regulate expression of major histocompatibility complex class I heavy chains

Jones¹,

Hanson²,

Sun³

et al. 1995

J Virol

255

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Reduction of major histocompatibility complex class I cell surface expression occurs in adenovirus-, herpes simplex virus-, human cytomegalovirus (HCMV)-, and murine cytomegalovirus-infected cell systems. Recently, it was demonstrated that the down-regulation mediated by HCMV infection is posttranslational, as a result of increased turnover of class I heavy chains in the endoplasmic reticulum (M. F. C. Beersma, M.

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Section: Discussionmentioning

confidence: 90%

Multiple independent loci within the human cytomegalovirus unique short region down-regulate expression of major histocompatibility complex class I heavy chains

Jones¹,

Hanson²,

Sun³

et al. 1995

J Virol

255

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“…Individuals at high risk for CMV disease include the immunologically immature fetus and newborn, patients undergoing immunosuppressive therapy for cancer or organ transplantation (24), and those with progressive immunodeficiency diseases, such as AIDS (20). Strict species specificity has hindered the study of human CMV (HCMV) in animals, and infection of mice with murine CMV (MCMV) has been used extensively as a model for studying the pathogenesis of CMV infection (8,34,46,57). The human and murine viruses are biologically similar in replication and pathogenesis (25,45) and have homologous genomes (52), which display similar genetic organizations and encode analogous gene products with similar functions (19,31,43,44,50,51,68).…”

mentioning

confidence: 99%

Murine cytomegalovirus with a deletion of genes spanning HindIII-J and -I displays altered cell and tissue tropism

Cavanaugh

Stenberg

Staley

et al. 1996

J Virol

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Murine cytomegalovirus (MCMV) gene products dispensable for growth in cell culture are likely to have important functions within the infected host, influencing tissue tropism, dissemination, or immunological responses against the virus. To identify such genes, our strategy was to delete large regions of the MCMV genome likely to contain genes nonessential for virus replication in NIH 3T3 cells. Mutant virus RV7 contained a deletion of 7.7 kb spanning portions of MCMV HindIII-J and -I. This virus grew comparably to wild-type (WT) virus in NIH 3T3 fibroblasts, primary embryo fibroblasts, and bone marrow macrophages. However, RV7 failed to replicate in target organs of immunocompetent BALB/c mice and severe combined immunodeficient mice, which are exquisitely sensitive to MCMV infection. This defect in in vivo growth may be related to the observation that RV7 grew poorly in the peritoneal macrophage cell line IC-21, which is highly permissive for growth of WT MCMV. Two other mutant viruses with an insertion or smaller deletion in the region common to the RV7 deletion grew comparably to WT virus in the macrophage cell line and replicated in salivary gland tissue. The poor growth of RV7 in IC-21 cells was due to a block in immediate-early gene expression, as levels of RNA from immediate-early gene IE1 were reduced eightfold compared with levels for WT virus in macrophages infected with RV7. Consequently, levels of RNA from early and late genes were also reduced. The lower expression of IE1 in RV7-infected IC-21 macrophages was not due to defective entry of virus into the cells, as equal amounts of viral DNA were present in cells 3 h after infection with RV7 or WT MCMV. These studies demonstrate that deletion of sequences in HindIII-J and -I confer altered cell and tissue tropism.Cells. Murine NIH 3T3 fibroblasts (American Type Culture Collection [ATCC] CRL1658; ATCC, Rockville, Md.) were propagated in Dulbecco's modified essential medium (DMEM; Mediatech, Herndon, Va.) supplemented with 10% heat-inactivated bovine calf serum (HyClone Laboratories, Logan, Utah) and 1% L-glutamine (Gibco/BRL, Grand Island, N.Y.). IC-21 cells, a simian virus 40-transformed peritoneal macrophage cell line derived from C57BL/6 mice (41), were obtained from ATCC and were propagated in RPMI medium (Mediatech) supplemented with 10% heat-inactivated fetal calf serum (Gibco/BRL) and 1% L-glutamine. Primary fibroblasts, derived from the embryos of timedpregnant BALB/c.ByJ mice (Jackson Laboratory, Bar Harbor, Maine) on day 19 of gestation, were cultured in DMEM containing 20% heat-inactivated fetal calf serum, 1% L-glutamine, and 50 g of gentamicin sulfate (Sigma Chemical Co., St. Louis, Mo.) per ml.Virus. The parental WT MCMV used in this study was of the Smith strain (ATCC VR-194). Stocks of WT and mutant viruses were prepared in and titers were determined on NIH 3T3 cells as previously described (8). Mock preparations of virus consisted of culture supernatants from noninfected NIH 3T3 cells.Mice. BALB/c.ByJ mice, either 20-day-old weanlings (...

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“…However, most CTL in both BALB/c and B6 mice actually recognize E and not IE Ags (15,(17)(18)(19). Thus, paradoxically, the Ags that would seem most likely to be affected by immunomodulatory genes actually elicit the majority of the immunodominant responses.…”

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confidence: 99%

The Murine Cytomegalovirus Immunomodulatory Gene m152 Prevents Recognition of Infected Cells by M45-Specific CTL But Does Not Alter the Immunodominance of the M45-Specific CD8 T Cell Response In Vivo

Gold

Munks

Wagner³

et al. 2002

The Journal of Immunology

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Although in vitro studies have shown that herpesviruses, including murine CMV (MCMV), encode genes that interfere with the MHC class I pathway, their effects on the CTL response in vivo is unclear. We identified a Db-restricted CTL epitope from MCMV M45 by screening an MCMV genomic library using CTL clones isolated from mice infected with MCMV lacking m152. Because m152 severely inhibits CTL recognition of M45 in vitro, we questioned whether an M45-specific response would be generated in mice infected with wild-type MCMV expressing m152. Mice infected with wild-type MCMV or MCMVΔm152 made similar responses to the M45 Ag. Moreover, we saw no skewing of the proportion of M45-specific CD8 T cells within the total MCMV-specific response after infection with MCMV with m152. Despite the profound effect m152 has on presentation of M45 in vitro, it does not affect the immunodominance of M45 in the CTL response in vivo.

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Murine cytomegalovirus-induced suppression of antigen-specific cytotoxic T lymphocyte maturation

Cited by 21 publications

References 29 publications

Multiple independent loci within the human cytomegalovirus unique short region down-regulate expression of major histocompatibility complex class I heavy chains

Multiple independent loci within the human cytomegalovirus unique short region down-regulate expression of major histocompatibility complex class I heavy chains

Murine cytomegalovirus with a deletion of genes spanning HindIII-J and -I displays altered cell and tissue tropism

The Murine Cytomegalovirus Immunomodulatory Gene m152 Prevents Recognition of Infected Cells by M45-Specific CTL But Does Not Alter the Immunodominance of the M45-Specific CD8 T Cell Response In Vivo

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