MiRNA Let-7 Family Regulated by NEAT1 and ARID3A/NF-κB Inhibits PRRSV-2 Replication in Vitro and in Vivo

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2022 Oct 10

PMID 36215225

Authors

Xiangbin You

Min Liu

Qian Liu

Huijuan Li

Yilin Qu

Xiaoxiao Gao

Chengyu Huang

Gan Luo

Gang Cao

Dequan Xu

Affiliations

Soon will be listed here.

Abstract

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically devastating diseases affecting the swine industry worldwide. To investigate the role of miRNAs in the infection and susceptibility of PRRS virus (PRRSV), twenty-four miRNA libraries were constructed and sequenced from PRRSV-infected and mock-infected Porcine alveolar macrophages (PAMs) of Meishan, Landrace, Pietrain and Qingping pigs at 9 hours post infection (hpi), 36 hpi, and 60 hpi. The let-7 family miRNAs were significantly differentially expressed between PRRSV-infected and mock-infected PAMs from 4 pig breeds. The let-7 family miRNAs could significantly inhibit PRRSV-2 replication by directly targeting the 3'UTR of the PRRSV-2 genome and porcine IL6, which plays an important role in PRRSV replication and lung injury. NEAT1 acts as a competing endogenous lncRNA (ceRNA) to upregulate IL6 by attaching let-7 in PAMs. EMSA and ChIP results confirmed that ARID3A could bind to the promoter region of pri-let-7a/let-7f/let-7d gene cluster and inhibit the expression of the let-7 family. Moreover, the NF-κB signaling pathway inhibits the expression of the let-7 family by affecting the nuclear import of ARID3A. The pEGFP-N1-let-7 significantly reduced viral infections and pathological changes in PRRSV-infected piglets. Taken together, NEAT1/ARID3A/let-7/IL6 play significant roles in PRRSV-2 infection and may be promising therapeutic targets for PRRS.

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References

Iliopoulos D, Hirsch H, Struhl K . An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell. 2009; 139(4):693-706. PMC: 2783826. DOI: 10.1016/j.cell.2009.10.014. View

Zhou Z, Li X, Liu J, Dong L, Chen Q, Liu J . Honeysuckle-encoded atypical microRNA2911 directly targets influenza A viruses. Cell Res. 2014; 25(1):39-49. PMC: 4650580. DOI: 10.1038/cr.2014.130. View

Shi H, Ma J, Mi C, Li J, Wang F, Lee J . Amorfrutin A inhibits TNF-α-induced NF-κB activation and NF-κB-regulated target gene products. Int Immunopharmacol. 2014; 21(1):56-62. DOI: 10.1016/j.intimp.2014.04.016. View

Yu M, Zheng X, Witschi H, Pinkerton K . The role of interleukin-6 in pulmonary inflammation and injury induced by exposure to environmental air pollutants. Toxicol Sci. 2002; 68(2):488-97. DOI: 10.1093/toxsci/68.2.488. View

Wensvoort G . Lelystad virus and the porcine epidemic abortion and respiratory syndrome. Vet Res. 1993; 24(2):117-24. View

Lee Y, Kim M, Han J, Yeom K, Lee S, Baek S . MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 2004; 23(20):4051-60. PMC: 524334. DOI: 10.1038/sj.emboj.7600385. View

Kim J, Cho I, Hong J, Choi Y, Kim H, Lee Y . Identification and characterization of new microRNAs from pig. Mamm Genome. 2008; 19(7-8):570-80. DOI: 10.1007/s00335-008-9111-3. View

Huang W, Huang M, Ouyang H, Peng J, Liang J . Oridonin inhibits vascular inflammation by blocking NF-κB and MAPK activation. Eur J Pharmacol. 2018; 826:133-139. DOI: 10.1016/j.ejphar.2018.02.044. View

Vincent A, Thacker B, Halbur P, Rothschild M, Thacker E . In vitro susceptibility of macrophages to porcine reproductive and respiratory syndrome virus varies between genetically diverse lines of pigs. Viral Immunol. 2005; 18(3):506-12. DOI: 10.1089/vim.2005.18.506. View

10.

Madapong A, Saeng-Chuto K, Chaikhumwang P, Tantituvanont A, Saardrak K, Pedrazuela Sanz R . Immune response and protective efficacy of intramuscular and intradermal vaccination with porcine reproductive and respiratory syndrome virus 1 (PRRSV-1) modified live vaccine against highly pathogenic PRRSV-2 (HP-PRRSV-2) challenge, either alone or.... Vet Microbiol. 2020; 244:108655. DOI: 10.1016/j.vetmic.2020.108655. View

11.

Liang W, Li Z, Wang P, Fan P, Zhang Y, Zhang Q . Differences of immune responses between Tongcheng (Chinese local breed) and Large White pigs after artificial infection with highly pathogenic porcine reproductive and respiratory syndrome virus. Virus Res. 2016; 215:84-93. DOI: 10.1016/j.virusres.2016.02.004. View

12.

Lunney J, Fang Y, Ladinig A, Chen N, Li Y, Rowland B . Porcine Reproductive and Respiratory Syndrome Virus (PRRSV): Pathogenesis and Interaction with the Immune System. Annu Rev Anim Biosci. 2015; 4:129-54. DOI: 10.1146/annurev-animal-022114-111025. View

13.

An J, Lv W, Zhang Y . LncRNA NEAT1 contributes to paclitaxel resistance of ovarian cancer cells by regulating ZEB1 expression via miR-194. Onco Targets Ther. 2017; 10:5377-5390. PMC: 5691924. DOI: 10.2147/OTT.S147586. View

14.

Wu X, Sui Z, Zhang H, Wang Y, Yu Z . Integrated Analysis of lncRNA-Mediated ceRNA Network in Lung Adenocarcinoma. Front Oncol. 2020; 10:554759. PMC: 7523091. DOI: 10.3389/fonc.2020.554759. View

15.

Wang S, Liu W, Yang L, Sargent C, Liu H, Wang C . Effects of FUT1 gene mutation on resistance to infectious disease. Mol Biol Rep. 2011; 39(3):2805-10. DOI: 10.1007/s11033-011-1039-0. View

16.

Liu X, Bai J, Jiang C, Song Z, Zhao Y, Nauwynck H . Therapeutic effect of Xanthohumol against highly pathogenic porcine reproductive and respiratory syndrome viruses. Vet Microbiol. 2019; 238:108431. DOI: 10.1016/j.vetmic.2019.108431. View

17.

Kuhn J, Lauck M, Bailey A, Shchetinin A, Vishnevskaya T, Bao Y . Reorganization and expansion of the nidoviral family Arteriviridae. Arch Virol. 2015; 161(3):755-68. PMC: 5573231. DOI: 10.1007/s00705-015-2672-z. View

18.

You X, Qu Y, Zhang Y, Huang J, Gao X, Huang C . Mir-331-3p Inhibits PRRSV-2 Replication and Lung Injury by Targeting PRRSV-2 ORF1b and Porcine α. Front Immunol. 2020; 11:547144. PMC: 7544944. DOI: 10.3389/fimmu.2020.547144. View

19.

Huang C, Bernard D, Zhu J, Dash R, Chu A, Knupp A . Small molecules block the interaction between porcine reproductive and respiratory syndrome virus and CD163 receptor and the infection of pig cells. Virol J. 2020; 17(1):116. PMC: 7392821. DOI: 10.1186/s12985-020-01361-7. View

20.

Lawson S, Rossow K, Collins J, Benfield D, Rowland R . Porcine reproductive and respiratory syndrome virus infection of gnotobiotic pigs: sites of virus replication and co-localization with MAC-387 staining at 21 days post-infection. Virus Res. 1998; 51(2):105-13. DOI: 10.1016/s0168-1702(97)00086-5. View