14-3-3ε Acts As a Proviral Factor in Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Infection

Overview

Journal Vet Res

Publisher Biomed Central

Specialty Veterinary Medicine

Date 2019 Mar 2

PMID 30819256

Citations 4

Authors

Shengliang Cao

Fangyuan Cong

Min Tan

Guofei Ding

Jiaqi Liu

Li Li

Yuzhong Zhao

Sidang Liu

Yihong Xiao

Affiliations

Soon will be listed here.

Abstract

The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) emerged in 2006 in China and caused great economic losses for the swine industry because of the lack of an effective vaccine. 14-3-3 proteins are generating significant interest as potential drug targets by allowing the targeting of specific pathways to elicit therapeutic effects in human diseases. In a previous study, 14-3-3s were identified to interact with non-structural protein 2 (NSP2) of PRRSV. In the present study, the specific subtype 14-3-3ε was confirmed to interact with NSP2 and play a role in the replication of the HP-PRRSV TA-12 strain. Knockdown of 14-3-3ε in Marc-145 cells and porcine alveolar macrophages (PAMs) caused a significant decrease in TA-12 replication, while stable overexpression of 14-3-3ε caused a significant increase in the replication of TA-12 and low pathogenic PRRSV (LP-PRRSV) CH-1R. The 14-3-3 inhibitor difopein also decreased TA-12 and CH-1R replication in Marc-145 cells and PAMs. These findings are consistent with 14-3-3ε acting as a proviral factor and suggest that 14-3-3ε siRNA and difopein are therapeutic candidates against PRRSV infection.

Citing Articles

Research Progress in Porcine Reproductive and Respiratory Syndrome Virus-Host Protein Interactions.

Zhang H, Sha H, Qin L, Wang N, Kong W, Huang L Animals (Basel). 2022; 12(11).

PMID: 35681845 PMC: 9179581. DOI: 10.3390/ani12111381.

The role of 14-3-3 proteins in cell signalling pathways and virus infection.

Liu J, Cao S, Ding G, Wang B, Li Y, Zhao Y J Cell Mol Med. 2021; 25(9):4173-4182.

PMID: 33793048 PMC: 8093981. DOI: 10.1111/jcmm.16490.

The tail domain of PRRSV NSP2 plays a key role in aggrephagy by interacting with 14-3-3ε.

Cao S, Liu J, Ding G, Shao Q, Wang B, Li Y Vet Res. 2020; 51(1):104.

PMID: 32811532 PMC: 7433210. DOI: 10.1186/s13567-020-00816-7.

Porcine Reproductive and Respiratory Syndrome Virus Structural Protein GP3 Regulates Claudin 4 To Facilitate the Early Stages of Infection.

Ding G, Liu J, Shao Q, Wang B, Feng J, Li Y J Virol. 2020; 94(20).

PMID: 32759320 PMC: 7527063. DOI: 10.1128/JVI.00124-20.

References

van Hemert M, Steensma H, van Heusden G . 14-3-3 proteins: key regulators of cell division, signalling and apoptosis. Bioessays. 2001; 23(10):936-46. DOI: 10.1002/bies.1134. View

Hopper S, White M, Twiddy N . An outbreak of blue-eared pig disease (porcine reproductive and respiratory syndrome) in four pig herds in Great Britain. Vet Rec. 1992; 131(7):140-4. DOI: 10.1136/vr.131.7.140. View

Helke K, Queen S, Tarwater P, Turchan-Cholewo J, Nath A, Zink M . 14-3-3 protein in CSF: an early predictor of SIV CNS disease. J Neuropathol Exp Neurol. 2005; 64(3):202-8. DOI: 10.1093/jnen/64.3.202. View

Benzinger A, Popowicz G, Joy J, Majumdar S, Holak T, Hermeking H . The crystal structure of the non-liganded 14-3-3sigma protein: insights into determinants of isoform specific ligand binding and dimerization. Cell Res. 2005; 15(4):219-27. DOI: 10.1038/sj.cr.7290290. View

Mhawech P . 14-3-3 proteins--an update. Cell Res. 2005; 15(4):228-36. DOI: 10.1038/sj.cr.7290291. View

Bridges D, Moorhead G . 14-3-3 proteins: a number of functions for a numbered protein. Sci STKE. 2005; 2005(296):re10. DOI: 10.1126/stke.2962005re10. View

Elazhary Y, Weber J, Bikour H, Morin M, Girard C . 'Mystery swine disease' in Canada. Vet Rec. 1991; 129(22):495-6. DOI: 10.1136/vr.129.22.495-b. View

Tzivion G, Gupta V, Kaplun L, Balan V . 14-3-3 proteins as potential oncogenes. Semin Cancer Biol. 2006; 16(3):203-13. DOI: 10.1016/j.semcancer.2006.03.004. View

Fujii K, Tanabe Y, Uchikawa H, Kobayashi K, Kubota H, Takanashi J . 14-3-3 protein detection in the cerebrospinal fluid of patients with influenza-associated encephalopathy. J Child Neurol. 2006; 21(7):562-5. DOI: 10.1177/08830738060210070502. View

10.

Yang X, Lee W, Sobott F, Papagrigoriou E, Robinson C, Grossmann J . Structural basis for protein-protein interactions in the 14-3-3 protein family. Proc Natl Acad Sci U S A. 2006; 103(46):17237-42. PMC: 1859916. DOI: 10.1073/pnas.0605779103. View

11.

Morin M, Robinson Y . Porcine reproductive and respiratory syndrome in Quebec. Vet Rec. 1991; 129(16):367-8. DOI: 10.1136/vr.129.16.367. View

12.

Li Y, Wang X, Bo K, Wang X, Tang B, Yang B . Emergence of a highly pathogenic porcine reproductive and respiratory syndrome virus in the Mid-Eastern region of China. Vet J. 2007; 174(3):577-84. DOI: 10.1016/j.tvjl.2007.07.032. View

13.

Tong G, Zhou Y, Hao X, Tian Z, An T, Qiu H . Highly pathogenic porcine reproductive and respiratory syndrome, China. Emerg Infect Dis. 2008; 13(9):1434-6. PMC: 2857295. DOI: 10.3201/eid1309.070399. View

14.

Wensvoort G, Terpstra C, Pol J, ter Laak E, Bloemraad M, de Kluyver E . Mystery swine disease in The Netherlands: the isolation of Lelystad virus. Vet Q. 1991; 13(3):121-30. DOI: 10.1080/01652176.1991.9694296. View

15.

Nielsen M, Luo X, Biteau B, Syverson K, Jasper H . 14-3-3 Epsilon antagonizes FoxO to control growth, apoptosis and longevity in Drosophila. Aging Cell. 2008; 7(5):688-99. PMC: 3851013. DOI: 10.1111/j.1474-9726.2008.00420.x. View

16.

Wu K, Liou J . Cyclooxygenase inhibitors induce colon cancer cell apoptosis Via PPARdelta --> 14-3-3epsilon pathway. Methods Mol Biol. 2009; 512:295-307. DOI: 10.1007/978-1-60327-530-9_16. View

17.

Beura L, Sarkar S, Kwon B, Subramaniam S, Jones C, Pattnaik A . Porcine reproductive and respiratory syndrome virus nonstructural protein 1beta modulates host innate immune response by antagonizing IRF3 activation. J Virol. 2009; 84(3):1574-84. PMC: 2812326. DOI: 10.1128/JVI.01326-09. View

18.

Neal C, Yu D . 14-3-3ζ as a prognostic marker and therapeutic target for cancer. Expert Opin Ther Targets. 2010; 14(12):1343-54. PMC: 3017465. DOI: 10.1517/14728222.2010.531011. View

19.

Liu H, Loo Y, Horner S, Zornetzer G, Katze M, Gale Jr M . The mitochondrial targeting chaperone 14-3-3ε regulates a RIG-I translocon that mediates membrane association and innate antiviral immunity. Cell Host Microbe. 2012; 11(5):528-37. PMC: 3358705. DOI: 10.1016/j.chom.2012.04.006. View

20.

Morales D, Skoulakis E, Acevedo S . 14-3-3s are potential biomarkers for HIV-related neurodegeneration. J Neurovirol. 2012; 18(5):341-53. PMC: 3763985. DOI: 10.1007/s13365-012-0121-2. View