Ruirui HU, Liang FENG, Tao GUO, Rui YAO, Yaxin LI, Xiaokui WANG, Taotao MI, Shengwei HU

Inhibition of CD46 Receptor by RNAi Enhances Cell Resistance to BVDV Infection

This study aimed to investigate the inhibition effect of CD46 on the replication of bovine viral diarrhea viruses (BVDV). BVDV causes bovine viral diarrheal mucosal disease, and prevention of BVDV infection is very important for livestock production. Here, we have designed four pairs of effective siRNAs, and in vitro experiments showed that some of them can effectively inhibit the expression of BVDV receptor CD46. Further results showed that BVDV replication was efficiently inhibited and the yield decreased accordingly when expression of CD46 was decreased by siRNA. In conclusion, this study provides a new approach to defend against BVDV infection.

CD46 Reseptörünün RNAi İnhibisyonu BVDV Enfeksiyonuna Hücre Direncini Artırır

Bu çalışmada, CD46’nın sığır viral diyare virüslerinin (BVDV) replikasyonu üzerindeki inhibisyon etkisinin araştırılması amaçlandı. BVDV, bovine viral diarrhea-mukozal hastalığa neden olur ve BVDV enfeksiyonunun önlenmesi hayvan yetiştiriciliği açısından oldukça önemlidir. Bu çalışmada, dört çift etkin siRNA tasarladık ve in vitro denemelerde bunlardan bazılarının BVDV reseptörü olan CD46 ekspresyonunu etkili bir şekilde inhibe edebildiği saptandı. Diğer sonuçlara bakıldığında, BVDV replikasyonunun etkin bir şekilde inhibe edildiği ve bu inhibisyonun siRNA tarafından azaltılan CD46 ekspresyonuna parallel şekillendiği belirlendi. Sonuç olarak, bu çalışma, BVDV enfeksiyonuna karşı savunmada yeni bir yaklaşım sunmaktadır.

PDF

___

1. Khodakaram-Tafti A, Farjanikish GH: Persistent bovine viral diarrhea virus (BVDV) infection in cattle herds. Iran J Vet Res, 18 (3): 154-163, 2017. DOI: 10.22099/ijvr.2017.4190

2. Garoussi MT, Mehrzad J, Nejati A: Investigation of persistent infection of bovine viral diarrhea virus (BVDV) in Holstein dairy cows. Trop Anim Health Prod, 51 (4): 853-858, 2019. DOI: 10.1007/s11250-018-1765-6

3. Reichel MP, Lanyon SR, Hill FI: Perspectives on current challenges and opportunities for bovine viral diarrhoea virus eradication in Australia and New Zealand. Pathogens, 7 (1): 14, 2018. DOI: 10.3390/pathogens7010014

4. Ridpath JF, Neill JD, Frey M, Landgraf JG: Phylogenetic, antigenic and clinical characterization of type 2 BVDV from North America. Vet Microbiol, 77 (1-2): 145-155, 2000. DOI: 10.1016/S0378-1135(00)00271-6

5. Islam F, Gopalan V, Lam AK: RNA interference-mediated gene silencing in esophageal adenocarcinoma. Methods Mol Biol, 1756, 269-279, 2018. DO: 10.1007/978-1-4939-7734-5_23

6. Caplen NJ, Zheng Z, Falgout B, Morgan RA: Inhibition of viral gene expression and replication in mosquito cells by dsRNA-triggered RNA interference. Mol Ther, 6 (2): 243-251, 2002. DOI: 10.1006/mthe.2002.0652

7. Adams R, Nicke B, Pohlenz H, Sohler F: Deciphering seed sequence based off-target effects in a large-scale RNAi reporter screen for e-cadherin expression. Plos One, 10 (9): e0137640, 2015. DOI: 10.1371/ journal.pone.0137640

8. Chen W, Yan W, Du Q, Fei L, Liu M, Ni Z, Sheng Z, Zheng Z: RNA interference targeting VP1 inhibits foot-and-mouth disease virus replication in BHK-21 cells and suckling mice. J Virol, 78 (13): 6900-6907, 2004. DOI: 10.1128/JVI.78.13.6900-6907.2004

9. Mccaffrey AP, Nakai H, Pandey K, Huang Z, Salazar FH, Xu H, Wieland SF, Marion PL, Kay MA: Inhibition of hepatitis B virus in mice by RNA interference. Nat Biotechnol, 21 (6): 639-644, 2003. DOI: 10.1038/nbt824

10. Ni W, Qiao J, Ma Q, Wang J, Wang D, Zhao X, Cao Y, Li Q, Hu S, Chen C: Development of sheep kidney cells with increased resistance to different subgenotypes of BVDV-1 by RNA interference. J Virol Methods, 218, 66-70, 2015. DOI: 10.1016/j.jviromet.2015.03.014

11. Alzamel N, Bayrou C, Decreux A, Desmecht D: Soluble forms of CD46 are detected in Bos taurus plasma and neutralize BVDV, the bovine pestivirus. Comp Immunol Microbiol Infect Dis, 49, 39-46, 2016. DOI: 10.1016/j.cimid.2016.09.001

12. Maurer K, Krey T, Moennig V, Thiel H, Rumenapf T: CD46 is a cellular receptor for bovine viral diarrhea virus. J Virol, 78 (4): 1792-1799, 2004. DOI: 10.1128/JVI.78.4.1792-1799.2004

13. Krey T, Moussay E, Thiel H, Rumenapf T: Role of the low-density lipoprotein receptor in entry of bovine viral diarrhea virus. J Virol, 80 (21): 10862-10867, 2006. DOI: 10.1128/JVI.01589-06

14. Liu YP, Von Eije KJ, Schopman NCT, Westerink J, Brake OT, Haasnoot J, Berkhout B: Combinatorial RNAi against HIV-1 using extended short hairpin RNAs. Mol Ther, 17 (10): 1712-1723, 2009. DOI: 10.1038/mt.2009.176

15. Luo J, Du J, Gao S, Zhang G, Sun J, Cong G, Shao J, Lin T, Chang H: Lentviral-mediated RNAi to inhibit target gene expression of the porcine integrin αv subunit, the FMDV receptor, and against FMDV infection in PK- 15 cells. Virol J, 8:428, 2011. DOI: 10.1186/1743-422X-8-428