The Experts below are selected from a list of 330 Experts worldwide ranked by ideXlab platform
D J Jeffries - One of the best experts on this subject based on the ideXlab platform.
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Molecular biology of varicella-zoster virus. A review prepared for the UK Advisory Group on Chickenpox.
The Journal of infection, 1998Co-Authors: D R Harper, R L Gilbert, D J JeffriesAbstract:Varicella-zoster virus (human herpesvirus 3; VZV) is one of eight herpes viruses that routinely infect humans. It is classified as a member of the genus Varicellovirus, subfamily Alphaherpesvirinae, family Herpesviridae. Of the other human herpes viruses it is most closely related to the herpes simplex viruses (also members of the Alphalerpesvirinae). Like all herpes viruses, the virus has a large double-stranded DNA genome within an icosahedral nucleocapsid. This is surrounded by a proteinaceous tegument and a trilaminar membrane derived from host-cell membranes into which the viral glycoproteins are inserted. The structure of the virion is summarized in Fig. 1.
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Molecular Biology of Varicella-zoster Virus: A review prepared for the UK Advisory Group on Chickenpox
Journal of Infection, 1998Co-Authors: D R Harper, R L Gilbert, D J JeffriesAbstract:Varicella-zoster virus (human herpesvirus 3; VZVI is one of eight viruses that routinely infect humans. It is classified as a member of the genus Varicellovirus , subfamily Alphaherpesvirinae , family Herpesviridae . Of the other human herpes viruses it is ost closely related to the herpes simplex viruses (also members of the Alphaherpesvirinae ). Like all herpes viruses, the virus has a large double-stranded DNA genome within an icosahedral nucleocapsid. This is surrounded by a proteinaceous tegument and a trilaminar memhbrane derived from host-cell membranes into which the viral glycoproteins are inserted. The structure of the virion is summarized in Fig. 1.
Morten Tryland - One of the best experts on this subject based on the ideXlab platform.
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Cervid herpesvirus 2 infection in reindeer: a review.
Veterinary microbiology, 2010Co-Authors: Carlos G. Das Neves, Etienne Thiry, Swaantje J. Roth, Espen Rimstad, Morten TrylandAbstract:Herpesviruses of the genus Varicellovirus are known to infect and cause disease in a variety of ruminant species, but the impact of cervid herpesvirus 2 (CvHV2) in reindeer (Rangifer tarandus) is mostly unknown. Reindeer is a circum-polar species with a total estimated number of more than 5 million animals. Mortality may reach high values, as in northern Norway, especially in calves (37%; 2005–2006), and disease can potentially account for some of this mortality. CvHV2 has been isolated during a natural outbreak of infectious keratoconjunctivitis, indicating an etiologal link. Serological screening has shown that CvHV2 infection is prevalent in Northern Norway and experimental infection studies have demonstrated that viremia, latency and vertical transmission occur for CvHV2. The present review aims at summarizing current knowledge on the epidemiology, pathogenesis and molecular virology of CvHV2.
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Evaluation of three commercial bovine ELISA kits for detection of antibodies against Alphaherpesviruses in reindeer (Rangifer tarandus tarandus)
Acta veterinaria Scandinavica, 2009Co-Authors: Carlos G. Das Neves, Espen Rimstad, Matthieu Roger, Nigel G. Yoccoz, Morten TrylandAbstract:Background The genus Varicellovirus (family Herpesviridae subfamily Alphaherpesvirinae) includes a group of viruses genetically and antigenically related to bovine herpesvirus 1 (BoHV-1) among which cervid herpesvirus 2 (CvHV-2) can be of importance in reindeer. These viruses are known to be responsible for different diseases in both wild and domestic animals. Reindeer are a keystone in the indigenous Saami culture and previous studies have reported the presence of antibodies against alphaherpesviruses in semi-domesticated reindeer in northern Norway. Mortality rates, especially in calves, can be very high in some herds and the abortion potential of alphaherpesvirus in reindeer, unlike in bovines, remains unknown. ELISA kits are the most used screening method in domestic ruminants and given the close genetic relationship between viruses within this genus, it might be possible to use such kits to screen cervids for different alphaherpesviruses. We have compared three different commercial ELISA kits in order to validate its use for reindeer and CvHV-2.
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Evaluation of three commercial bovine ELISA kits for detection of antibodies against Alphaherpesviruses in reindeer (Rangifer tarandus tarandus)
Acta Veterinaria Scandinavica, 2009Co-Authors: Carlos G Das Neves, Espen Rimstad, Matthieu Roger, Nigel G. Yoccoz, Morten TrylandAbstract:Background The genus Varicellovirus (family Herpesviridae subfamily Alphaherpesvirinae ) includes a group of viruses genetically and antigenically related to bovine herpesvirus 1 (BoHV-1) among which cervid herpesvirus 2 (CvHV-2) can be of importance in reindeer. These viruses are known to be responsible for different diseases in both wild and domestic animals. Reindeer are a keystone in the indigenous Saami culture and previous studies have reported the presence of antibodies against alphaherpesviruses in semi-domesticated reindeer in northern Norway. Mortality rates, especially in calves, can be very high in some herds and the abortion potential of alphaherpesvirus in reindeer, unlike in bovines, remains unknown. ELISA kits are the most used screening method in domestic ruminants and given the close genetic relationship between viruses within this genus, it might be possible to use such kits to screen cervids for different alphaherpesviruses. We have compared three different commercial ELISA kits in order to validate its use for reindeer and CvHV-2. Methods Three commercial bovine ELISA kits (A, B and C), using either indirect (A) or blocking (B and C) ELISA techniques to detect antibodies against BoHV-1 were tested with sera from 154 reindeer in order to detect antibodies against CvHV-2. A Spearman's rank-based coefficient of correlation (ρ) was calculated. A dilution trial was performed for all kits. A virus neutralization test using both BoHV-1 and CvHV-2 was carried out. Results Seroprevalence was almost the same with all kits (40–41%). Despite a similar qualitative score, quantitatively kits classified samples differently and a strong correlation was only identified between Kits B and C. Blocking kits performed better in both repeatability and in the dilution trial. The virus neutralization results confirmed the ELISA results to a very high degree. Neutralizing titres ranged from 1:2 to 1:256 and from 0 to 1:16 against CvHV-2 and BoHV-1 respectively. Conclusion Results show that the genetic and antigenic similarity between BoHV-1 and CvHV-2 enables the use of a bovine gB blocking ELISA kit to screen reindeer. The use of an ELISA kit is both cheaper and time saving, allowing screening of large populations. This study revealed a high number of positive animals against CvHV-2 and its impact and distribution in the general population should be further evaluated.
Danijela Koppers-lalic - One of the best experts on this subject based on the ideXlab platform.
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Structural and functional analysis of the TAP-inhibiting UL49.5 proteins of Varicelloviruses
Molecular Immunology, 2011Co-Authors: Marieke C. Verweij, Maaike E. Ressing, Danijela Koppers-lalic, Joachim Koch, Andrea D. Lipińska, Edwin Quinten, Jessica Funke, Hans C. Van Leeuwen, Krystyna Bieńkowska-szewczyk, Emmanuel J. H. J. WiertzAbstract:Viral infections are counteracted by virus-specific cytotoxic T cells that recognize the infected cell via MHC class I (MHC I) molecules presenting virus-derived peptides. The loading of the peptides onto MHC I molecules occurs in the endoplasmic reticulum (ER) and is facilitated by the peptide loading complex. A key player in this complex is the transporter associated with antigen processing (TAP), which translocates the viral peptides from the cytosol into the ER. Herpesviruses have developed many strategies to evade cytotoxic T cells. Several members of the genus Varicellovirus encode a UL49.5 protein that prevents peptide transport through TAP. These include bovine herpesvirus (BoHV) 1, BoHV-5, bubaline herpesvirus 1, cervid herpesvirus 1, pseudorabies virus, felid herpesvirus 1, and equine herpesvirus 1 and 4. BoHV-1 UL49.5 inhibits TAP by preventing conformational changes essential for peptide transport and by inducing degradation of the TAP complex. UL49.5 consists of an ER luminal N-terminal domain, a transmembrane domain and a cytosolic C-terminal tail domain. In this study, the following features of UL49.5 were deciphered: (1) chimeric constructs of BoHV-1 and VZV UL49.5 attribute the lack of TAP inhibition by VZV UL49.5 to its ER-luminal domain, (2) the ER-luminal and TM domains of UL49.5 are required for efficient interaction with and inhibition of TAP, (3) the C-terminal RXRX sequence is essential for TAP degradation by BoHV-1 UL49.5, and (4) in addition to the RXRX sequence, the cytoplasmic tail of BoHV-1 UL49.5 carries a motif that is required for efficient TAP inhibition by the protein. A model is presented depicting how the different domains of UL49.5 may block the translocation of peptides by TAP and target TAP for proteasomal degradation.
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The Capacity of UL49.5 Proteins To Inhibit TAP Is Widely Distributed among Members of the Genus Varicellovirus
Journal of Virology, 2010Co-Authors: Marieke C. Verweij, Andrea D. Lipińska, Wouter F. Van Leeuwen, Krystyna Bieńkowska-szewczyk, Maaike E. Ressing, Danijela Koppers-lalic, Ilhem Messaoudi, Paul R Kinchington, Jeffrey I Cohen, Frans A.m. RijsewijkAbstract:The lifelong infection by Varicelloviruses is characterized by a fine balance between the host immune response and immune evasion strategies used by these viruses. Virus-derived peptides are presented to cytotoxic T lymphocytes by major histocompatibility complex (MHC) class I molecules. The transporter associated with antigen processing (TAP) transports the peptides from the cytosol into the endoplasmic reticulum, where the loading of MHC-I molecules occurs. The Varicelloviruses bovine herpesvirus 1 (BoHV-1), pseudorabies virus, and equid herpesviruses 1 and 4 have been found to encode a UL49.5 protein that inhibits TAP-mediated peptide transport. To investigate to what extent UL49.5-mediated TAP inhibition is conserved within the family of Alphaherpesvirinae, the homologs of another five Varicelloviruses, one mardivirus, and one iltovirus were studied. The UL49.5 proteins of BoHV-5, bubaline herpesvirus 1, cervid herpesvirus 1, and felid herpesvirus 1 were identified as potent TAP inhibitors. The varicella-zoster virus and simian Varicellovirus UL49.5 proteins fail to block TAP; this is not due to the absence of viral cofactors that might assist in this process, since cells infected with these viruses did not show reduced TAP function either. The UL49.5 homologs of the mardivirus Marek's disease virus 1 and the iltovirus infectious laryngotracheitis virus did not block TAP, suggesting that the capacity to inhibit TAP via UL49.5 has been acquired by Varicelloviruses only. A phylogenetic analysis of viruses that inhibit TAP through their UL49.5 proteins reveals an interesting hereditary pattern, pointing toward the presence of this capacity in defined clades within the genus Varicellovirus.
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The Varicellovirus UL49.5 Protein Blocks the Transporter Associated with Antigen Processing (TAP) by Inhibiting Essential Conformational Transitions in the 6+6 Transmembrane TAP Core Complex
Journal of immunology (Baltimore Md. : 1950), 2008Co-Authors: Marieke C. Verweij, Danijela Koppers-lalic, Edwin Quinten, Sandra Loch, Florian Klauschies, Paul J. Lehner, Arend Mulder, Michael R. Knittler, Robert Tampé, Joachim KochAbstract:TAP translocates virus-derived peptides from the cytosol into the endoplasmic reticulum, where the peptides are loaded onto MHC class I molecules. This process is crucial for the detection of virus-infected cells by CTL that recognize the MHC class I-peptide complexes at the cell surface. The Varicellovirus bovine herpesvirus 1 encodes a protein, UL49.5, that acts as a potent inhibitor of TAP. UL49.5 acts in two ways, as follows: 1) by blocking conformational changes of TAP required for the translocation of peptides into the endoplasmic reticulum, and 2) by targeting TAP1 and TAP2 for proteasomal degradation. At present, it is unknown whether UL49.5 interacts with TAP1, TAP2, or both. The contribution of other members of the peptide-loading complex has not been established. Using TAP-deficient cells reconstituted with wild-type and recombinant forms of TAP1 and TAP2, TAP was defined as the prime target of UL49.5 within the peptide-loading complex. The presence of TAP1 and TAP2 was required for efficient interaction with UL49.5. Using deletion mutants of TAP1 and TAP2, the 6+6 transmembrane core complex of TAP was shown to be sufficient for UL49.5 to interact with TAP and block its function. However, UL49.5-induced inhibition of peptide transport was most efficient in cells expressing full-length TAP1 and TAP2. Inhibition of TAP by UL49.5 appeared to be independent of the presence of other peptide-loading complex components, including tapasin. These results demonstrate that UL49.5 acts directly on the 6+6 transmembrane TAP core complex of TAP by blocking essential conformational transitions required for peptide transport.
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Varicellovirus UL49.5 Proteins Differentially Affect the Function of the Transporter Associated with Antigen Processing, TAP
PLoS pathogens, 2008Co-Authors: Danijela Koppers-lalic, Marieke C. Verweij, Joachim Koch, Andrea D. Lipińska, Ying Wang, Edwin Quinten, Eric Reits, Sandra Loch, Marisa Marcondes Rezende, Franz DausAbstract:Cytotoxic T-lymphocytes play an important role in the protection against viral infections, which they detect through the recognition of virus-derived peptides, presented in the context of MHC class I molecules at the surface of the infected cell. The transporter associated with antigen processing (TAP) plays an essential role in MHC class I–restricted antigen presentation, as TAP imports peptides into the ER, where peptide loading of MHC class I molecules takes place. In this study, the UL49.5 proteins of the Varicelloviruses bovine herpesvirus 1 (BHV-1), pseudorabies virus (PRV), and equine herpesvirus 1 and 4 (EHV-1 and EHV-4) are characterized as members of a novel class of viral immune evasion proteins. These UL49.5 proteins interfere with MHC class I antigen presentation by blocking the supply of antigenic peptides through inhibition of TAP. BHV-1, PRV, and EHV-1 recombinant viruses lacking UL49.5 no longer interfere with peptide transport. Combined with the observation that the individually expressed UL49.5 proteins block TAP as well, these data indicate that UL49.5 is the viral factor that is both necessary and sufficient to abolish TAP function during productive infection by these viruses. The mechanisms through which the UL49.5 proteins of BHV-1, PRV, EHV-1, and EHV-4 block TAP exhibit surprising diversity. BHV-1 UL49.5 targets TAP for proteasomal degradation, whereas EHV-1 and EHV-4 UL49.5 interfere with the binding of ATP to TAP. In contrast, TAP stability and ATP recruitment are not affected by PRV UL49.5, although it has the capacity to arrest the peptide transporter in a translocation-incompetent state, a property shared with the BHV-1 and EHV-1 UL49.5. Taken together, these results classify the UL49.5 gene products of BHV-1, PRV, EHV-1, and EHV-4 as members of a novel family of viral immune evasion proteins, inhibiting TAP through a variety of mechanisms.
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The Varicellovirus-Encoded TAP Inhibitor UL49.5 Regulates the Presentation of CTL Epitopes by Qa-1b1
Journal of immunology (Baltimore Md. : 1950), 2007Co-Authors: Thorbald Van Hall, Danijela Koppers-lalic, Sandra Laban, Joachim Koch, Calin Precup, Patrick S. Asmawidjaja, Rienk Offringa, Emmanuel J. H. J. WiertzAbstract: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-1 b 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.
D R Harper - One of the best experts on this subject based on the ideXlab platform.
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Molecular biology of varicella-zoster virus. A review prepared for the UK Advisory Group on Chickenpox.
The Journal of infection, 1998Co-Authors: D R Harper, R L Gilbert, D J JeffriesAbstract:Varicella-zoster virus (human herpesvirus 3; VZV) is one of eight herpes viruses that routinely infect humans. It is classified as a member of the genus Varicellovirus, subfamily Alphaherpesvirinae, family Herpesviridae. Of the other human herpes viruses it is most closely related to the herpes simplex viruses (also members of the Alphalerpesvirinae). Like all herpes viruses, the virus has a large double-stranded DNA genome within an icosahedral nucleocapsid. This is surrounded by a proteinaceous tegument and a trilaminar membrane derived from host-cell membranes into which the viral glycoproteins are inserted. The structure of the virion is summarized in Fig. 1.
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Molecular Biology of Varicella-zoster Virus: A review prepared for the UK Advisory Group on Chickenpox
Journal of Infection, 1998Co-Authors: D R Harper, R L Gilbert, D J JeffriesAbstract:Varicella-zoster virus (human herpesvirus 3; VZVI is one of eight viruses that routinely infect humans. It is classified as a member of the genus Varicellovirus , subfamily Alphaherpesvirinae , family Herpesviridae . Of the other human herpes viruses it is ost closely related to the herpes simplex viruses (also members of the Alphaherpesvirinae ). Like all herpes viruses, the virus has a large double-stranded DNA genome within an icosahedral nucleocapsid. This is surrounded by a proteinaceous tegument and a trilaminar memhbrane derived from host-cell membranes into which the viral glycoproteins are inserted. The structure of the virion is summarized in Fig. 1.
Marieke C. Verweij - One of the best experts on this subject based on the ideXlab platform.
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Alignments of the amino acid sequences of selected herpesvirus-encoded TAP-inhibitors.
2015Co-Authors: Marieke C. Verweij, Maaike E. Ressing, Daniëlle Horst, Bryan D. Griffin, Rutger D. Luteijn, Andrew J. Davison, Emmanuel J. H. J. WiertzAbstract:A) simplexvirus ICP47 orthologs, B) simplexvirus (upper 5 lines) and Varicellovirus (lower 12 lines) UL49.5 orthologs, C) cytomegalovirus US6 orthologs, and D) lymphocryptovirus BNLF2a orthologs. The alignments of predicted primary translation products were made using ClustalW, followed by manual adjustment. The number of residues in each sequence is shown on the right. Green highlights residues that are conserved in all sequences, and yellow highlights residues that are conserved in a majority. Bold N residues in US6 indicate potential N-linked glycosylation sites. An illustrationof sequence disposition is shown below each alignment, with approximate boundaries displayed.
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The Capacity of UL49.5 Proteins To Inhibit TAP Is Widely Distributed among Members of the Genus Varicellovirus
Journal of Virology, 2010Co-Authors: Marieke C. Verweij, Andrea D. Lipińska, Wouter F. Van Leeuwen, Krystyna Bieńkowska-szewczyk, Maaike E. Ressing, Danijela Koppers-lalic, Ilhem Messaoudi, Paul R Kinchington, Jeffrey I Cohen, Frans A.m. RijsewijkAbstract:The lifelong infection by Varicelloviruses is characterized by a fine balance between the host immune response and immune evasion strategies used by these viruses. Virus-derived peptides are presented to cytotoxic T lymphocytes by major histocompatibility complex (MHC) class I molecules. The transporter associated with antigen processing (TAP) transports the peptides from the cytosol into the endoplasmic reticulum, where the loading of MHC-I molecules occurs. The Varicelloviruses bovine herpesvirus 1 (BoHV-1), pseudorabies virus, and equid herpesviruses 1 and 4 have been found to encode a UL49.5 protein that inhibits TAP-mediated peptide transport. To investigate to what extent UL49.5-mediated TAP inhibition is conserved within the family of Alphaherpesvirinae, the homologs of another five Varicelloviruses, one mardivirus, and one iltovirus were studied. The UL49.5 proteins of BoHV-5, bubaline herpesvirus 1, cervid herpesvirus 1, and felid herpesvirus 1 were identified as potent TAP inhibitors. The varicella-zoster virus and simian Varicellovirus UL49.5 proteins fail to block TAP; this is not due to the absence of viral cofactors that might assist in this process, since cells infected with these viruses did not show reduced TAP function either. The UL49.5 homologs of the mardivirus Marek's disease virus 1 and the iltovirus infectious laryngotracheitis virus did not block TAP, suggesting that the capacity to inhibit TAP via UL49.5 has been acquired by Varicelloviruses only. A phylogenetic analysis of viruses that inhibit TAP through their UL49.5 proteins reveals an interesting hereditary pattern, pointing toward the presence of this capacity in defined clades within the genus Varicellovirus.
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Unmasking the masters of evasion : TAP inhibition by Varicellovirus UL49.5 proteins
2010Co-Authors: Marieke C. VerweijAbstract:The life-long infection by Varicelloviruses is characterized by a fine balance between the host immune response and immune evasion strategies employed by these viruses. Virus-derived peptides are presented to cytotoxic T-lymphocytes by MHC I molecules. The transporter associated with antigen processing (TAP) transports the peptides from the cytosol into the endoplasmic reticulum, where the loading of MHC I molecules occurs. The UL49.5 protein of the Varicelloviruse bovine herpesvirus 1 (BHV-1) is a potent inhibitor of TAP-mediated peptide transport. The viral protein prevents MHC I maturation by rendering the TAP complex in a translocation incompetent state. In addition, TAP proteins are degraded in the presence of BHV-1 UL49.5. The chapters 2 to 4 of this thesis focus on the functional dissection of BoHV-1 UL49.5 and aim to identify its target domain within the TAP complex. All herpesviruses sequenced to date code for a UL49.5 homolog. However, in chapter 5 and 6 we show that only a few viruses belonging to the genus Varicellovirus encode a TAP-inhibiting UL49.5. The applicability of the UL49.5 proteins to study and modify pathways of antigen presentation is demonstrated in chapter 7 and 8. Chapter 9 describes the identification of a TAP inhibitor in cowpox virus
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Varicellovirus UL49.5 Proteins Differentially Affect the Function of the Transporter Associated with Antigen Processing, TAP
PLoS pathogens, 2008Co-Authors: Danijela Koppers-lalic, Marieke C. Verweij, Joachim Koch, Andrea D. Lipińska, Ying Wang, Edwin Quinten, Eric Reits, Sandra Loch, Marisa Marcondes Rezende, Franz DausAbstract:Cytotoxic T-lymphocytes play an important role in the protection against viral infections, which they detect through the recognition of virus-derived peptides, presented in the context of MHC class I molecules at the surface of the infected cell. The transporter associated with antigen processing (TAP) plays an essential role in MHC class I–restricted antigen presentation, as TAP imports peptides into the ER, where peptide loading of MHC class I molecules takes place. In this study, the UL49.5 proteins of the Varicelloviruses bovine herpesvirus 1 (BHV-1), pseudorabies virus (PRV), and equine herpesvirus 1 and 4 (EHV-1 and EHV-4) are characterized as members of a novel class of viral immune evasion proteins. These UL49.5 proteins interfere with MHC class I antigen presentation by blocking the supply of antigenic peptides through inhibition of TAP. BHV-1, PRV, and EHV-1 recombinant viruses lacking UL49.5 no longer interfere with peptide transport. Combined with the observation that the individually expressed UL49.5 proteins block TAP as well, these data indicate that UL49.5 is the viral factor that is both necessary and sufficient to abolish TAP function during productive infection by these viruses. The mechanisms through which the UL49.5 proteins of BHV-1, PRV, EHV-1, and EHV-4 block TAP exhibit surprising diversity. BHV-1 UL49.5 targets TAP for proteasomal degradation, whereas EHV-1 and EHV-4 UL49.5 interfere with the binding of ATP to TAP. In contrast, TAP stability and ATP recruitment are not affected by PRV UL49.5, although it has the capacity to arrest the peptide transporter in a translocation-incompetent state, a property shared with the BHV-1 and EHV-1 UL49.5. Taken together, these results classify the UL49.5 gene products of BHV-1, PRV, EHV-1, and EHV-4 as members of a novel family of viral immune evasion proteins, inhibiting TAP through a variety of mechanisms.
