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

Jones, Thomas R.; Hanson, Laura K.; Sun, Lei; Slater, Jacquelyn S.; Stenberg, R M; Campbell, Andann E.

doi:10.1128/jvi.69.8.4830-4841.1995

Cited by 256 publications

(96 citation statements)

References 53 publications

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“…In one instance, antigen presentation of a specific viral antigen, the major immediate early protein, is inhibited by another viral protein, pp65 (37), In other examples, however, MHC class I antigen presentation is inhibited globally i,e, both virus-derived and cellular antigens are no longer presented. This involves several genes, as was first observed by Jones, Campbell and colleagues, who analyzed mutant viruses with deletions in the unique shore (US) region which were nonessential for growth in tissue culture (38), MHC class I antigen presentation was restored in infected cells when US genes belonging to a family of eight glycoproceins with low homol-ogy were deleted. From this gene family, the four glycoproteins US2, US3, US6 and USi I independently affected the intracellular transport of MHC class I molecules (39), Interestingly, each of these glycoproteins seems to operate differently US2 and USl 1 interfere with MHC class I assembly immediately after heavy chain translocation into the ER (40), By an unknown mechanism they reverse the translocation of the glycosylated heavy chains through the translocation channel SEC61 (41), Once in the cytosol, the heavy chains are deglycosylated and degraded by the proteasome (40).…”

Section: Viral Immune Escape Mechanisms Targeting the Mhc Class I Antmentioning

confidence: 82%

A comparison of viral immune escape strategies targeting the MHC class I assembly pathway

Früh¹,

Gruhler²,

Krishna³

et al. 1999

Immunological Reviews

105

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Peptide fragments from proteins of intracellular pathogens such as viruses are displayed at the cell surface by MHC class I molecules thus enabling surveillance by cytotoxic T cells. Peptides are produced in the cytosol by proteasomal degradation and translocated into the endoplasmic reticulum by the peptide transporter TAP. Empty MHC class I molecules associate with TAP prior to their acquisition of peptides, a process which is assisted and controlled by a series of chaperones. The first part of this review summarizes our current knowledge of this assembly pathway and describes recent observations that tapasin functions as an endoplasmic reticulum retention molecule for empty MHC class I molecules. To defeat the presentation of virus-derived peptides, several DNA viruses have devised strategies to interfere with MHC class I assembly. Although these evasion strategies have evolved independently and differ mechanistically they often target the same step in this pathway. We compare escape mechanisms of different viruses with particular emphasis on the retention of newly synthesized MHC class I molecules in the endoplasmic reticulum and the inhibition of peptide transport by viral proteins.

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Section: Viral Immune Escape Mechanisms Targeting the Mhc Class I Antmentioning

confidence: 82%

A comparison of viral immune escape strategies targeting the MHC class I assembly pathway

Früh¹,

Gruhler²,

Krishna³

et al. 1999

Immunological Reviews

105

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“…Perturbation of this delicate balance leads to life-threatening infections in immunocompromised patients, transplant recipients and infected newborns and illustrates how the outcome of this host-virus relationship is dependent on viral manipulation of the host immune response (Hengel et al, 1998;Klenerman and Hill, 2005). The several HCMV-encoded immunoevasins (Jones et al, 1995) are presumably aimed primarily, but not solely, at control of the CD8 þ T cell and NK cell responses (Falk et al, 2002;Mocarski, 2004;Pinto and Hill, 2005;Yewdell and Hill, 2002). Here we will discuss the HCMV immunoevasins that interfere with class I MHC antigen presentation, US3, US6, US10, US2, US11, UL16, UL18, UL40, UL141, and UL142.…”

Section: Human Cytomegalovirusmentioning

confidence: 99%

“…US2 and US11 catalyze destruction of class I MHC HCs from the ER membrane by targeting them to the Ub-proteasome system (Wiertz et al, 1996a,b), a process we discuss in detail in a later section. Expression of each individual immunoevasin results in reduction of cell surface expression of class I MHC peptide-loaded complexes and evasion of CD8 þ T cell-mediated lysis (Ahn et al, 1996;Jones et al, 1995).…”

Section: Hcmv Interference With Class I Mhc Antigen Presentationmentioning

confidence: 99%

Antigen Presentation and the Ubiquitin‐Proteasome System in Host–Pathogen Interactions

Loureiro

Ploegh

2006

Advances in Immunology

160

122

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Relatively small genomes and high replication rates allow viruses and bacteria to accumulate mutations. This continuously presents the host immune system with new challenges. On the other side of the trenches, an increasingly well-adjusted host immune response, shaped by coevolutionary history, makes a pathogen's life a rather complicated endeavor. It is, therefore, no surprise that pathogens either escape detection or modulate the host immune response, often by redirecting normal cellular pathways to their advantage. For the purpose of this chapter, we focus mainly on the manipulation of the class I and class II major histocompatibility complex (MHC) antigen presentation pathways and the ubiquitin (Ub)-proteasome system by both viral and bacterial pathogens. First, we describe the general features of antigen presentation pathways and the Ub-proteasome system and then address how they are manipulated by pathogens. We discuss the many human cytomegalovirus (HCMV)-encoded immunomodulatory genes that interfere with antigen presentation (immunoevasins) and focus on the HCMV immunoevasins US2 and US11, which induce the degradation of class I MHC heavy chains by the proteasome by catalyzing their export from the endoplasmic reticulum (ER)-membrane into the cytosol, a process termed ER dislocation. US2- and US11-mediated subversion of ER dislocation ensures proteasomal degradation of class I MHC molecules and presumably allows HCMV to avoid recognition by cytotoxic T cells, whilst providing insight into general aspects of ER-associated degradation (ERAD) which is used by eukaryotic cells to purge their ER of defective proteins. We discuss the similarities and differences between the distinct pathways co-opted by US2 and US11 for dislocation and degradation of human class I MHC molecules and also a putatively distinct pathway utilized by the murine herpes virus (MHV)-68 mK3 immunoevasin for ER dislocation of murine class I MHC. We speculate on the implications of the three pathogen-exploited dislocation pathways to cellular ER quality control. Moreover, we discuss the ubiquitin (Ub)-proteasome system and its position at the core of antigen presentation as proteolysis and intracellular trafficking rely heavily on Ub-dependent processes. We add a few examples of manipulation of the Ub-proteasome system by pathogens in the context of the immune system and such diverse aspects of the host-pathogen relationship as virus budding, bacterial chromosome integration, and programmed cell death, to name a few. Finally, we speculate on newly found pathogen-encoded deubiquitinating enzymes (DUBs) and their putative roles in modulation of host-pathogen interactions.

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“…236 These inhibitory activities tap into peptide generation (UL83), 237,238 peptide processing by means of luminal endoplasmic reticulum aminopeptidase (US4-1), 239 antigenic peptide translocation by the transporter associated with antigen processing complex (US6), 240,241 peptide-major histocompatibility complex formation (UL82), 242 and major histocompatibility complex-I and -II presentation at the cell surface (US3, US11, US2, and US10). [243][244][245][246][247][248][249][250][251] These lytic gene products are either expressed at immediately early or early phases of infection, or are imported into the infected cells as virion structural tegument proteins. The key to containing bacterial pathogens in the oral cavity is the recruitment and activation of neutrophils at the site of infection.…”

Section: Cytomegalovirusmentioning

confidence: 99%

Herpesvirus‐bacteria synergistic interaction in periodontitis

Chen

Feng

Slots

2019

Periodontology 2000

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The etiopathogenesis of severe periodontitis includes herpesvirus‐bacteria coinfection. This article evaluates the pathogenicity of herpesviruses (cytomegalovirus and Epstein‐Barr virus) and periodontopathic bacteria (Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis) and coinfection of these infectious agents in the initiation and progression of periodontitis. Cytomegalovirus and A. actinomycetemcomitans/P. gingivalis exercise synergistic pathogenicity in the development of localized (“aggressive”) juvenile periodontitis. Cytomegalovirus and Epstein‐Barr virus are associated with P. gingivalis in adult types of periodontitis. Periodontal herpesviruses that enter the general circulation may also contribute to disease development in various organ systems. A 2‐way interaction is likely to occur between periodontal herpesviruses and periodontopathic bacteria, with herpesviruses promoting bacterial upgrowth, and bacterial factors reactivating latent herpesviruses. Bacterial‐induced gingivitis may facilitate herpesvirus colonization of the periodontium, and herpesvirus infections may impede the antibacterial host defense and alter periodontal cells to predispose for bacterial adherence and invasion. Herpesvirus‐bacteria synergistic interactions, are likely to comprise an important pathogenic determinant of aggressive periodontitis. However, mechanistic investigations into the molecular and cellular interaction between periodontal herpesviruses and bacteria are still scarce. Herpesvirus‐bacteria coinfection studies may yield significant new discoveries of pathogenic determinants, and drug and vaccine targets to minimize or prevent periodontitis and periodontitis‐related systemic diseases.

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

Cited by 256 publications

References 53 publications

A comparison of viral immune escape strategies targeting the MHC class I assembly pathway

A comparison of viral immune escape strategies targeting the MHC class I assembly pathway

Antigen Presentation and the Ubiquitin‐Proteasome System in Host–Pathogen Interactions

Herpesvirus‐bacteria synergistic interaction in periodontitis

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