Suppression of a Subset of Interferon-Induced Genes by Human Papillomavirus Type 16 E7 via a Cyclin Dependent Kinase 8-Dependent Mechanism
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cloning of E7 Mutants
2.2. Cell Culture and Creation of Cell Lines
2.3. Cellular Growth Rates
2.4. RNA Extraction, RT-qPCR, and Western Blotting
2.5. RNA Sequencing
2.6. siRNA Transfection
2.7. Immunoprecipitation
2.8. Chromatin Immunoprecipitation
2.9. Statistics
3. Results
3.1. The CR3 of E7 Contributes to Episomal Maintenance of the HPV16 Genome
3.2. E7 F57A Is Defective in E7-Mediated Suppression of ISGs
3.3. E7 May Function Downstream of JAK Activation to Suppress Interferon-Stimulated Gene Expression
3.4. E7 Does not Regulate STAT Activation
3.5. CDK8 Associates with E7 and Contributes to ISG Suppression
3.6. CDK8 Occupies the Promoters of Interferon-Stimulated Genes
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Genotype | Number of Samples | Episomal | Integrated | Fraction Episomal | p Value (Wt v Mutant) |
---|---|---|---|---|---|
HPV16 (wild type) | 51 | 40 | 11 | 0.78 | |
M84S | 8 | 4 | 4 | 0.50 | 0.18 |
G85A | 6 | 3 | 3 | 0.50 | 0.15 |
Y52A | 10 | 5 | 5 | 0.50 | 0.11 |
ED80-81KK | 5 | 2 | 3 | 0.40 | 0.09 |
D62K | 7 | 3 | 4 | 0.43 | 0.07 |
N53D | 12 | 6 | 6 | 0.50 | 0.07 |
S63D | 9 | 3 | 6 | 0.33 | <0.05 |
QKP96-98EEA | 11 | 3 | 8 | 0.27 | <0.01 |
V55T | 13 | 4 | 9 | 0.31 | <0.01 |
T64D | 7 | 1 | 6 | 0.14 | <0.01 |
R77E | 7 | 0 | 7 | 0.00 | <0.001 |
R66E | 13 | 2 | 11 | 0.15 | <0.0001 |
F57A | 34 | 6 | 28 | 0.18 | <0.0001 |
Pathway Name | # Entities Found | # Entities Total | Entities FDR |
---|---|---|---|
Interferon alpha/beta signaling | 10 | 184 | <0.0001 |
Interferon Signaling | 10 | 392 | <0.0001 |
Cytokine Signaling in Immune system | 11 | 1055 | <0.001 |
Transport of fatty acids | 2 | 18 | 0.01 |
Transport of vitamins, nucleosides, and related molecules | 3 | 100 | 0.02 |
Upregulated | Downregulated | ||
---|---|---|---|
Gene ID | Fold Change | Gene ID | Fold Change |
SLC44A5 | 5713.3 | ARL2-SNX15 | −4881.7 |
GPAT2 | 3410.2 | AC013489.1 | −4599.3 |
SLC27A6 | 170.4 | AC139530.2 | −4185.4 |
VAV1 | 147.7 | UGT1A3 | −4061.3 |
IFI27 | 49.3 | AC097658.1 | −441.7 |
KRBOX1 | 47.7 | USP32P2 | −102.9 |
IFI44L | 34.3 | MTND1P23 | −69.8 |
XAF1 | 29.8 | SHC1P1 | −59.0 |
IFI6 | 23.7 | FOXF2 | -49.8 |
MX2 | 22.6 | MAMLD1 | −43.6 |
FYB1 | 19.5 | FAM103A2P | −30.7 |
FAM26E | 19.1 | SPINK7 | −30.1 |
BST2 | 17.7 | RAB4B-EGLN2 | −30.0 |
AL163051.1 | 10.6 | SPRR4 | −28.9 |
AC009268.2 | 8.1 | AC008556.1 | −26.6 |
AL136295.5 | 7.6 | VASH2 | −21.7 |
AL450992.2 | 7.4 | SORD2P | −18.7 |
PART1 | 3.4 | LYPD2 | −17.7 |
AC010326.4 | 3.1 | SEPT7P7 | −17.2 |
AC022400.7 | 2.5 | PKNOX2 | −14.2 |
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Rice, S.; Kim, S.-m.; Rodriguez, C.; Songock, W.; Raikhy, G.; Lopez, R.; Henderson, L.; Yusufji, A.; Bodily, J. Suppression of a Subset of Interferon-Induced Genes by Human Papillomavirus Type 16 E7 via a Cyclin Dependent Kinase 8-Dependent Mechanism. Viruses 2020, 12, 311. https://doi.org/10.3390/v12030311
Rice S, Kim S-m, Rodriguez C, Songock W, Raikhy G, Lopez R, Henderson L, Yusufji A, Bodily J. Suppression of a Subset of Interferon-Induced Genes by Human Papillomavirus Type 16 E7 via a Cyclin Dependent Kinase 8-Dependent Mechanism. Viruses. 2020; 12(3):311. https://doi.org/10.3390/v12030311
Chicago/Turabian StyleRice, Sadie, Seong-man Kim, Cynthia Rodriguez, William Songock, Gaurav Raikhy, Rebecca Lopez, Lauren Henderson, Arjun Yusufji, and Jason Bodily. 2020. "Suppression of a Subset of Interferon-Induced Genes by Human Papillomavirus Type 16 E7 via a Cyclin Dependent Kinase 8-Dependent Mechanism" Viruses 12, no. 3: 311. https://doi.org/10.3390/v12030311