Convergent Evolution by Cancer and Viruses in Evading the NKG2D Immune Response
Abstract
:Simple Summary
Abstract
1. Introduction
1.1. NKG2D Receptor and NK Cell Activation
1.2. NKG2D Ligands
1.3. Evading Detection by NKG2D
2. NKG2DL Expression in Healthy Cells and Autoimmunity
2.1. Cell Stress Induces NKG2DL mRNA and Protein Expression
2.2. Post-Transcriptional Regulation of NKG2DL Expression During Cell Stress
3. NKG2DL Expression Is Induced in Virally Infected Cells
4. Virus Immune Evasion
4.1. Viral Proteins Use a Range of Strategies to Downregulate NKG2DL Expression
4.2. Viral Strategies to Evade Pattern Recognition Receptors
4.3. Viruses Can Use miRNAs to Regulate NKG2DL Expression at a Post-Transcriptional Level
4.4. Virus-Mediated Shedding of NKG2DL
4.5. Virus-Mediated Immune Subversion
4.6. Evolution of Viral Immune Evasion has Converged on Disrupting the NKG2D System
5. NKG2DL Expression in Transformed Cells
5.1. Tumours Upregulate NKG2DLs via Chronic DDR
5.2. NKG2DLs Are Upregulated in Tumours Through Deregulation of the Cell Cycle and Activated Cell Signalling
6. Cancer Strategies to Evade NKG2D
6.1. Loss of NKG2DLs May Be Involved in Metastatic Progression
6.2. Downregulation of NKG2Ds on Immune Cells by Cell-Bound and Soluble NKG2DLs
6.3. Mechanisms of NKG2DL Shedding by Tumour Cells
6.4. Soluble NKG2DLs Affect Other Immune Cell Types
6.5. Tumours Use miRNAs to Downregulate NKG2DL Expression at the Post-Transcriptional Level
6.6. Other Strategies Used by Tumours Subvert the NKG2D Immune Response
7. Viral and Cancer Immune Evasion Strategies Converge on the NKG2D Response
8. Strategies Employed by the Immune System to Counter Viral and Tumour Immune Evasion
9. Conclusions and Outlook
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Virus | Immunoevasin | Mechanism | Reference |
---|---|---|---|
MCMV | gp40 | Downregulation of surface RAE-1α-γ expression | [63] |
m155 | Targets H60 for degradation | [64] | |
m145 | Downregulation of MULT1 surface expression | [65] | |
Fcr-1 | Downregulation of MULT1 and H60 surface expression | [66] | |
HCMV | UL16 | Retention of MICB, ULBP2 and ULBP3 in ER and cis-Golgi apparatus | [13,67,68,69,70] |
UL142 | Retention of MICA in cis-Golgi apparatus | [25,71,72] | |
US9 | Targets MICA *008 for degradation | [73] | |
US12, US13, US18, US20 | Target MICA, MICB and ULBP2 for degradation | [74,75] | |
miR-UL112 | Targets 3′ UTR of MICA and MICB transcripts, causing mRNA destabilisation | [37,89] | |
miR-US25-2-3p | Downregulation of TIMP3, causing increasing shedding by ADAM17 and MMP14 Shedding | [93] | |
VZV | Unknown | Downregulation of ULBP2 and ULBP3 by unknown mechanism | [76] |
HSV-1 | Late viral gene product(s) | Downregulation of MICA, ULBP1, ULBP2 and ULBP3 (cell-dependent) at a post-translational stage | [76,77] |
miR-H8 | Disrupts expression of GPI-anchoring machinery, reducing ULBP2 and ULBP3 surface expression | [92] | |
HHV-7 | U21 | Targets ULBP1 for degradation and downregulates MICA and MICB by unknown mechanism | [78] |
HHV-6 | Early viral gene product(s) | Targets MICB, ULBP1 and ULBP3 for degradation | [79] |
KSHV | K5 | Ubiquitinylates MICA, causing redistribution from surface | [80] |
miR-K12-7 | Targets 3′ UTR of MICB transcripts, causing mRNA destabilisation | [90] | |
EBV | miR-BART2-5p | Targets 3′ UTR of MICB transcripts, causing mRNA destabilisation | [90] |
HBV | HBx | Forms complex with GATA-2/3 to repress MICA and MICB transcription | [83] |
HBc | Binds to CpG islands in MICA/B promoters to repress transcription | [83] | |
HCV | NS3/4a | Decreases MICA and MICB by unknown mechanism | [81] |
NS5a | Stimulates immunosuppressive cytokine production and NKG2D receptor downregulation | [96] | |
Ad5 | E3/19K | Retention of MICA and MICB in ER | [82] |
HIV-1 | Nef | Downregulation of MICA, ULBP1 and ULBP2 | [84] |
Vif | Degradation of A3G, preventing DDR-mediated NKG2DL expression | [88] | |
Unknown | Shedding of MICA, MICB and ULBP2 by host MMP shedding | [94] | |
VSV | Unknown | Unknown (post-transcriptional) | [86] |
VV | EL3 | Prevents detection of dsRNA viral genome from PRRs | [87] |
PyVs (JCV and BK) | miR-J1-3p | Targets 3′ UTR of ULBP3 mRNA and prevents translation | [91] |
ZPXV | OMCP | Antagonism of NKG2D receptor | [95] |
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Baugh, R.; Khalique, H.; Seymour, L.W. Convergent Evolution by Cancer and Viruses in Evading the NKG2D Immune Response. Cancers 2020, 12, 3827. https://doi.org/10.3390/cancers12123827
Baugh R, Khalique H, Seymour LW. Convergent Evolution by Cancer and Viruses in Evading the NKG2D Immune Response. Cancers. 2020; 12(12):3827. https://doi.org/10.3390/cancers12123827
Chicago/Turabian StyleBaugh, Richard, Hena Khalique, and Leonard W. Seymour. 2020. "Convergent Evolution by Cancer and Viruses in Evading the NKG2D Immune Response" Cancers 12, no. 12: 3827. https://doi.org/10.3390/cancers12123827