Herpes Simplex Virus Type 2 ICP47 Inhibits Human TAP but Not Mouse TAP

Tomazin, Roman; Schoot, N E G van; Goldsmith, Kimberley; Jugovic, Pieter; Sempé, Pascal; Früh, Klaus; Johnson, David C.

doi:10.1128/jvi.72.3.2560-2563.1998

Cited by 110 publications

(51 citation statements)

References 11 publications

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“…For HSV-1-based oncolytic viruses such as T-VEC, strategies have also been devised to enhance immune responses by deleting the HSV-1 protein ICP47. ICP47 blocks the function of TAP (transporter associated with antigen processing) and thus prevents infected cells from presenting antigen to CD8 + T cells 84 .…”

Section: Cathepsin-mediated Death Pathwaymentioning

confidence: 99%

Oncolytic viruses: a new class of immunotherapy drugs

Kaufman

Kohlhapp

Zloza

2015

Nat Rev Drug Discov

1,229

1,097

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Oncolytic viruses represent a new class of therapeutic agents that promote anti-tumour responses through a dual mechanism of action that is dependent on selective tumour cell killing and the induction of systemic anti-tumour immunity. The molecular and cellular mechanisms of action are not fully elucidated but are likely to depend on viral replication within transformed cells, induction of primary cell death, interaction with tumour cell antiviral elements and initiation of innate and adaptive anti-tumour immunity. A variety of native and genetically modified viruses have been developed as oncolytic agents, and the approval of the first oncolytic virus by the US Food and Drug Administration (FDA) is anticipated in the near future. This Review provides a comprehensive overview of the basic biology supporting oncolytic viruses as cancer therapeutic agents, describes oncolytic viruses in advanced clinical trials and discusses the unique challenges in the development of oncolytic viruses as a new class of drugs for the treatment of cancer.

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Section: Cathepsin-mediated Death Pathwaymentioning

confidence: 99%

Oncolytic viruses: a new class of immunotherapy drugs

Kaufman

Kohlhapp

Zloza

2015

Nat Rev Drug Discov

1,229

1,097

View full text Add to dashboard Cite

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“…Eventually these empty MHC class I molecules are translocated into the cytosol for degradation by the ubiquitin/proteasome pathway, which seems to be the usual fate of MHC class I molecules which do not acquire peptides (65). ICP47 is unable to inhibit murine TAP (66), which might have important imphcations for mouse models of HSV infection. This specificity seems to be encoded by the TAP2 subunit of TAP, since ICP47 inhibits mouse or rat TAP 1 co-transfected with human TAP2 in TAP deficient T2 cells (R Momburg, personal communication).…”

Section: Viral Tap Inhibitorsmentioning

confidence: 99%

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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“…ICP47 effectively blocks the major histocompatibility complex class I (MHC I) antigen presentation pathway. ICP47 binds with high affinity to the human transporter associated with antigen presentation (TAP) and blocks its binding of antigenic peptides [25]. Association of ICP47 precludes substrate binding and prevents nucleotide-binding domain closure necessary for ATP hydrolysis.…”

Section: Anti-tumor Mechanism Of Oncolytic Virusmentioning

confidence: 99%

Oncolytic Herpes Simplex Virus ICP47 Deletion Reverses Tumor Immune Evasion

Cheng¹,

Wang²,

Zhang³

et al. 2018

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Herpes simplex virus (HSV) is an enveloped, double-stranded DNA virus that has been used with modification as oncolytic viruses (OVs) against a number of tumor types. OVs represent a new class of therapeutic agents that promote anti-tumour responses through a dual mechanism of action that is dependent on selective tumor cell killing and the induction of systemic anti-tumour immunity. Among OVs, HSVs preferentially replicate in and lyse cancer cells, leading to in situ autovaccination, adaptive anti-virus and anti-tumor immunity. Suppression of antitumor immunity after OV therapy has been observed and the molecular and cellular mechanisms of action are recently reported. ICP47, a small protein produced by the herpes simplex virus, is considered as an important factor in the evasion of cellular immune responses in HSV-infected cells. Therefore, reviewing the research status of ICP47 is certainly helpful to improve the anti-tumor effect of oncolytic HSVs (oHSVs). Here, this review will focus on the following contents: 1) Anti-tumor mechanism of OVs; 2) Functions of early HSV genes; 3) The mechanism of immune escape of ICP47; 4) Recombinant HSV against cancer; 5) The functional verification of ICP47 deletion. This review highlights the current understanding of recombinant HSVs against cancers.

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Herpes Simplex Virus Type 2 ICP47 Inhibits Human TAP but Not Mouse TAP

Cited by 110 publications

References 11 publications

Oncolytic viruses: a new class of immunotherapy drugs

Oncolytic viruses: a new class of immunotherapy drugs

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

Oncolytic Herpes Simplex Virus ICP47 Deletion Reverses Tumor Immune Evasion

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