Varicelloviruses avoid T cell recognition by UL49.5-mediated inactivation of the transporter associated with antigen processing

Koppers-Lalić, Danijela; Reits, Eric; Ressing, Maaike E.; Lipińska, Andrea D.; Abele, Rupert; Koch, Joachim; Rezende, Marisa Marcondes; Admiraal, Pieter; Leeuwen, Daphne van; Bieńkowska-Szewczyk, Krystyna; Mettenleiter, Thomas C.; Rijsewijk, F.A.M.; Tampé, Robert; Neefjes, Jacques; Wiertz, Emmanuel J. H. J.

doi:10.1073/pnas.0501463102

Cited by 166 publications

(257 citation statements)

References 51 publications

(75 reference statements)

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“…In order to diminish the detection and the elimination of virus-infected cells by cytotoxic T lymphocytes, BoHV-1 was shown to down-regulate antigen presentation by the class I major histocompatibility complex (MHC class I) [95,96,115,146]. Two independent mechanisms are responsible for down-regulation of MHC class I molecules.…”

Section: Immune Response and Immune Evasion Strategiesmentioning

confidence: 99%

“…Two independent mechanisms are responsible for down-regulation of MHC class I molecules. UL49.5 by blocking the transporter associated with antigen processing (TAP) [96] and vhs protein (encoded by UL41) [95] act together in this inhibition. But they are not able to completely prevent the immune detection of BoHV-1 infected cells.…”

Section: Immune Response and Immune Evasion Strategiesmentioning

confidence: 99%

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Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis

et al. 2007

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-Bovine herpesvirus 1 (BoHV-1), classified as an alphaherpesvirus, is a major pathogen of cattle. Primary infection is accompanied by various clinical manifestations such as infectious bovine rhinotracheitis, abortion, infectious pustular vulvovaginitis, and systemic infection in neonates. When animals survive, a life-long latent infection is established in nervous sensory ganglia. Several reactivation stimuli can lead to viral re-excretion, which is responsible for the maintenance of BoHV-1 within a cattle herd. This paper focuses on an updated pathogenesis based on a molecular characterization of BoHV-1 and the description of the virus cycle. Special emphasis is accorded to the impact of the latency and reactivation cycle on the epidemiology and the control of BoHV-1. Several European countries have initiated BoHV-1 eradication schemes because of the significant losses incurred by disease and trading restrictions. The vaccines used against BoHV-1 are described in this context where the differentiation of infected from vaccinated animals is of critical importance to achieve BoHV-1 eradication.

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Section: Immune Response and Immune Evasion Strategiesmentioning

confidence: 99%

Section: Immune Response and Immune Evasion Strategiesmentioning

confidence: 99%

Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis

et al. 2007

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“…In the pseudorabies virus, an additional glycoprotein, designated gN (UL49.5), is a glycosylated 10 kDa transmembrane protein and is identified as an immune evasion molecule inhibiting the transporter associated with antigen processing (TAP) driven peptide import into the endoplasmic reticulum. The UL49.5 homologue encoded by BoHV-1 has the same immune evasion function, but is not classified as glycoprotein N [66].…”

Section: Viral Glycoproteinsmentioning

confidence: 99%

“…Alphaherpesviruses, like other herpesviruses, are able to interfere with the host's innate and adaptative immune responses. A growing list of immune evasion mechanisms is described [139], such as, for example, inhibition of TAP proteins [66] or Fc receptor activity of viral glycoproteins [43].…”

Section: Pathogenesis and Clinical Signsmentioning

confidence: 99%

Ruminant alphaherpesviruses related to bovine herpesvirus 1

et al. 2006

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-Herpesviruses have mainly co-evolved with their hosts for millions of years. Consequently, different related host species may have been infected by various genetically related herpesviruses. Illustrating this concept, several ruminant alphaherpesviruses have been shown to form a cluster of viruses closely related to bovine herpesvirus 1 (BoHV-1): namely bovine herpesvirus 5, bubaline herpesvirus 1, caprine herpesvirus 1, cervid herpesviruses 1 and 2 and elk herpesvirus 1. These viruses share common antigenic properties and the serological relationships between them can be considered as a threat to BoHV-1 eradication programmes. BoHV-1 is a herpesvirus responsible for infectious bovine rhinotracheitis, which is a disease of major economic concern. In this article, the genetic properties of these ruminant alphaherpesviruses are reviewed on a comparative basis and the issue of interspecific recombination is assessed. The pathogenesis of these infections is described with emphasis on the host range and crossing of the host species barrier. Indeed, the non bovine ruminant species susceptible to these ruminant alphaherpesviruses may be potential BoHV-1 reservoirs. The differential diagnosis of these related infections is also discussed. In addition, available epidemiological data are used to assess the potential of cross-infection in ruminant populations. A better knowledge of these ruminant alphaherpesvirus infections is essential to successfully control infectious bovine rhinotracheitis.

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“…Colon carcinomas C26 and CC36 were derived from the BALB/c stain and MC38 was derived from the C57BL/6 strain (39). Introduction of the UL49.5 gene from BHV1 was established by retroviral gene transduction with the LZRS vector containing an internal ribosome entry site and GFP, as described before (21). Cells with the highest GFP expression were positively sorted by FACS.…”

Section: Cell Linesmentioning

confidence: 99%

The Varicellovirus-Encoded TAP Inhibitor UL49.5 Regulates the Presentation of CTL Epitopes by Qa-1b1

Hall

Laban

Koppers-Lalić

et al. 2007

The Journal of Immunology

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Impairment of MHC class I Ag processing is a commonly observed mechanism that allows viruses and tumors to escape immune destruction by CTL. The peptide transporter TAP that is responsible for the delivery of MHC class I-binding peptides into the endoplasmic reticulum is a pivotal target of viral-immune evasion molecules, and expression of this transporter is frequently lost in advanced cancers. We recently described a novel population of CTL that intriguingly exhibits reactivity against such tumor-immune escape variants and that recognizes self-peptides emerging at the cell surface due to defects in the processing machinery. Investigations of this new type of CTL epitopes are hampered by the lack of an efficient inhibitor for peptide transport in mouse cells. In this article, we demonstrate that the varicellovirus protein UL49.5, in contrast to ICP47 and US6, strongly impairs the activity of the mouse transporter and mediates degradation of mouse TAP1 and TAP2. Inhibition of TAP was witnessed by a strong reduction of surface MHC class I display and a decrease in recognition of conventional tumor-specific CTL. Analysis of CTL reactivity through the nonclassical molecule Qa-1b revealed that the presentation of the predominant leader peptide was inhibited. Interestingly, expression of UL49.5 in processing competent tumor cells induced the presentation of the new category of peptides. Our data show that the varicellovirus UL49.5 protein is a universal TAP inhibitor that can be exploited for preclinical studies on CTL-based immune intervention.

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Varicelloviruses avoid T cell recognition by UL49.5-mediated inactivation of the transporter associated with antigen processing

Abstract: Detection and elimination of virus-infected cells by cytotoxic T lymphocytes depends on recognition of virus-derived peptides

Cited by 166 publications

References 51 publications

Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis

Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis

Ruminant alphaherpesviruses related to bovine herpesvirus 1

The Varicellovirus-Encoded TAP Inhibitor UL49.5 Regulates the Presentation of CTL Epitopes by Qa-1b1

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