KIF5B-mediated internalization of FMDV promotes virus infection

Wei Zhang; Fan Yang; Yang Yang; Weijun Cao; Wenhua Shao; Jiali Wang; Mengyao Huang; Zhitong Chen; Xiaoyi Zhao; Weiwei Li; Zixiang Zhu; Haixue Zheng

doi:10.1016/j.virs.2024.03.005

June 2024

Citation: Wei Zhang, Fan Yang, Yang Yang, Weijun Cao, Wenhua Shao, Jiali Wang, Mengyao Huang, Zhitong Chen, Xiaoyi Zhao, Weiwei Li, Zixiang Zhu, Haixue Zheng. KIF5B-mediated internalization of FMDV promotes virus infection .VIROLOGICA SINICA, 2024, 39(3) : 378-389. http://dx.doi.org/10.1016/j.virs.2024.03.005

KIF5B-mediated internalization of FMDV promotes virus infection

Wei Zhang ^a,b ,
Fan Yang ^a,b ,
Yang Yang ^a,b ,
Weijun Cao ^a,b ,
Wenhua Shao ^a,b ,
Jiali Wang ^a,b ,
Mengyao Huang ^a,b ,
Zhitong Chen ^a,b ,
Xiaoyi Zhao ^a,b ,
Weiwei Li ^a,b ,
Zixiang Zhu ^a,b ,
Haixue Zheng ^{a,b
,,}

a. State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730000, China;
b. Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou 730046, China

Corresponding author: Haixue Zheng, zhenghaixue@caas.cn
Received Date: 21 September 2023
Accepted Date: 13 March 2024
Available online: 16 March 2024

Abstract

Foot-and-mouth disease (FMD) is a highly contagious and economically important disease, which is caused by the FMD virus (FMDV). Although the cell receptor for FMDV has been identified, the specific mechanism of FMDV internalization after infection remains unknown. In this study, we found that kinesin family member 5B (KIF5B) plays a vital role during FMDV internalization. Moreover, we confirmed the interaction between KIF5B and FMDV structural protein VP1 by co-immunoprecipitation (Co-IP) and co-localization in FMDV-infected cells. In particular, the stalk [amino acids (aa) 413-678] domain of KIF5B was indispensable for KIF5B-VP1 interaction. Moreover, overexpression of KIF5B dramatically enhanced FMDV replication; consistently, knockdown or knockout of KIF5B suppressed FMDV replication. Furthermore, we also demonstrated that KIF5B promotes the internalization of FMDV via regulating clathrin uncoating. KIF5B also promotes the transmission of viral particles to early and late endosomes during the early stages of infection. In conclusion, our results demonstrate that KIF5B promotes the internalization of FMDV via regulating clathrin uncoating and intracellular transport. This study may provide a new therapeutic target for developing FMDV antiviral drugs.
- FMDV
- , VP1 protein
- , KIF5B
- , Endosome
- , Clathrin

Electronic Supplementary Material

10.1016j.virs.2024.03.005-ESM.docx
References
1. Bai, X., Bao, H., Li, P., Wei, W., Zhang, M., Sun, P., Cao, Y., Lu, Z., Fu, Y., Xie, B., Chen, Y., Li, D., Luo, J., Liu, Z., 2014. Effects of two amino acid substitutions in the capsid proteins on the interaction of two cell-adapted PanAsia-1 strains of foot-and-mouth disease virus serotype O with heparan sulfate receptor. Virol. J. 11, 132.
2. Bananis, E., Murray, J.W., Stockert, R.J., Satir, P., Wolkoff, A.W., 2000. Microtubule and motor-dependent endocytic vesicle sorting in vitro. Mol. Biol. Cell 11, 354a-355a.
3. Chen, S.Y., Yang, F., Zhu, Z.X., Cao, W.J., Lian, K.Q., Zhang, W., Zhu, Z.J., He, J.J., Guo, J.H., Liu, X.T., Zhou, B., Zheng, H.X., 2022. The endocytosis of foot-and mouth disease virus requires clathrin and caveolin and is dependent on the existence of Rab5 and Rab7 in CHO-677 cells. Vet. Microbiol. 274.
4. Conforti, L., Buckmaster, E.A., Tarlton, A., Brown, M.C., Lyon, M.F., Perry, V.H., Coleman, M.P., 1999. The major brain isoform of Kif1b lacks the putative mitochondria-binding domain. Mamm. Genome 10, 617-622.
5. Diefenbach, R.J., Diefenbach, E., Douglas, M.W., Cunningham, A.L., 2002. The heavy chain of conventional kinesin interacts with the SNARE proteins SNAP25 and SNAP23. Biochemistry-Us 41, 14906-14915.
6. Diefenbach, R.J., Mackay, J.P., Armati, P.J., Cunningham, A.L., 1998. The C-terminal region of the stalk domain of ubiquitous human kinesin heavy chain contains the binding site for kinesin light chain. Biochemistry-Us 37, 16663-16670.
7. Diwaker, D., Murray, J.W., Barnes, J., Wolkoff, A.W., Wilson, D.W., 2020. Deletion of the Pseudorabies Virus gE/gI-US9p complex disrupts kinesin KIF1A and KIF5C recruitment during egress, and alters the properties of microtubule-dependent transport in vitro. PLoS Pathog. 16, e1008597.
8. DuRaine, G., Wisner, T.W., Howard, P., Johnson, D.C., 2018. Kinesin-1 proteins KIF5A, -5B, and -5C promote anterograde transport of herpes simplex virus enveloped virions in axons. J. Virol. 92.
9. Feng, Q., Yu, H., Liu, Y., He, C., Hu, J., Sang, H., Ding, N., Ding, M., Fung, Y.W., Lau, L.T., Yu, A.C., Chen, J., 2004. Genome comparison of a novel foot-and-mouth disease virus with other FMDV strains. Biochem. Biophys. Res. Commun. 323, 254-263.
10. Gamarnik, A.V., Andino, R., 1998. Switch from translation to RNA replication in a positive-stranded RNA virus. Genes Dev. 12, 2293-2304.
11. Gao, W.N.D., Carpentier, D.C.J., Ewles, H.A., Lee, S.A., Smith, G.L., 2017. Vaccinia virus proteins A36 and F12/E2 show strong preferences for different kinesin light chain isoforms. Traffic 18, 505-518.
12. Hirokawa, N., Noda, Y., Tanaka, Y., Niwa, S., 2009. Kinesin superfamily motor proteins and intracellular transport. Nat. Rev. Mol. Cell Biol. 10, 682-696.
13. Hirokawa, N., Takemura, R., 2005. Molecular motors and mechanisms of directional transport in neurons. Nat. Rev. Neurosci. 6, 201-214.
14. Iworima, D.G., Pasqualotto, B.A., Rintoul, G.L., 2016. Kif5 regulates mitochondrial movement, morphology, function and neuronal survival. Mol. Cell. Neurosci. 72, 22-33.
15. Jackson, T., Clark, S., Berryman, S., Burman, A., Cambier, S., Mu, D., Nishimura, S., King, A.M., 2004. Integrin alphavbeta8 functions as a receptor for foot-and-mouth disease virus: role of the beta-chain cytodomain in integrin-mediated infection. J. Virol. 78, 4533-4540.
16. Jackson, T., Mould, A.P., Sheppard, D., King, A.M., 2002. Integrin alphavbeta1 is a receptor for foot-and-mouth disease virus. J. Virol. 76, 935-941.
17. Jackson, T., Sheppard, D., Denyer, M., Blakemore, W., King, A.M., 2000. The epithelial integrin alphavbeta6 is a receptor for foot-and-mouth disease virus. J. Virol. 74, 4949-4956.
18. Jordens, I., Marsman, M., Kuijl, C., Neefjes, J., 2005. Rab proteins, connecting transport and vesicle fusion. Traffic 6, 1070-1077.
19. Lawrence, P., Pacheco, J.M., Uddowla, S., Hollister, J., Kotecha, A., Fry, E., Rieder, E., 2013. Foot-and-mouth disease virus (FMDV) with a stable FLAG epitope in the VP1 G-H loop as a new tool for studying FMDV pathogenesis. Virology 436, 150-161.
20. Lawrence, P., Schafer, E.A., Rieder, E., 2012. The nuclear protein Sam68 is cleaved by the FMDV 3C protease redistributing Sam68 to the cytoplasm during FMDV infection of host cells. Virology 425, 40-52.
21. Liu, H., Xue, Q., Zhu, Z., Yang, F., Cao, W., Liu, X., Zheng, H., 2021. Foot-and-mouth disease virus inhibits RIP2 protein expression to promote viral replication. Virol. Sin. 36, 608-622.
22. Lou, J.X., Liu, Y.Y., Bai, J.S., Cheng, Y., Zhang, J., Liu, C.C., Zhou, B., 2023. Kinesin-1 regulates endocytic trafficking of classical swine fever virus along acetylated microtubules. J. Virol. 97, e0192922.
23. Mahy, B.W.J., 2005. Introduction and history of foot-and-mouth disease virus. Curr. Top. Microbiol. Immunol. 288, 1-8.
24. Malikov, V., da Silva, E.S., Jovasevic, V., Bennett, G., de Souza Aranha Vieira, D.A., Schulte, B., Diaz-Griffero, F., Walsh, D., Naghavi, M.H., 2015. HIV-1 capsids bind and exploit the kinesin-1 adaptor FEZ1 for inward movement to the nucleus. Nat. Commun. 6, 6660.
25. Martin-Acebes, M.A., Gonzalez-Magaldi, M., Sandvig, K., Sobrino, F., Armas-Portela, R., 2007. Productive entry of type C foot-and-mouth disease virus into susceptible cultured cells requires clathrin and is dependent on the presence of plasma membrane cholesterol. Virology 369, 105-118.
26. Nakata, T., Hirokawa, N., 2003. Microtubules provide directional cues for polarized axonal transport through interaction with kinesin motor head. J. Cell Biol. 162, 1045-1055.
27. Neff, S., Mason, P.W., Baxt, B., 2000. High-efficiency utilization of the bovine integrin alpha(v)beta(3) as a receptor for foot-and-mouth disease virus is dependent on the bovine beta(3) subunit. J. Virol. 74, 7298-7306.
28. Neff, S., Sa-Carvalho, D., Rieder, E., Mason, P.W., Blystone, S.D., Brown, E.J., Baxt, B., 1998. Foot-and-mouth disease virus virulent for cattle utilizes the integrin alpha(v)beta3 as its receptor. J. Virol. 72, 3587-3594.
29. Ni, Y.X., Zhou, N., Xue, W.Q., Rong, L., Yung, W.H., Lin, R.Z., Kao, R.Y., Duan, Z.G., Sun, H.T., Gong, H.R., Tang, X.M., Liu, M.F., Zhang, W., Qi, S., Chung, S., Song, Y.Q., Huang, J.D., 2018. A new role of anterograde motor Kif5b in facilitating large clathrin-coated vesicle mediated endocytosis via regulating clathrin uncoating. Cell Discov. 4, 65.
30. O'Donnell, V., Larocco, M., Baxt, B., 2008. Heparan sulfate-binding foot-and-mouth disease virus enters cells via caveola-mediated endocytosis. J. Virol. 82, 9075-9085.
31. Reed, L.J., Muench, H., 1938. A simple method of estimating fifty per cent endpoints12. Am. J. Epidemiol. 27, 493-497.
32. Scherer, J., Yi, J., Vallee, R.B., 2020. Role of cytoplasmic dynein and kinesins in adenovirus transport. FEBS Lett. 594, 1838-1847.
33. Su, Q.N., Cai, Q., Gerwin, C., Smith, C.L., Sheng, Z.H., 2004. Syntabulin is a microtubule-associated protein implicated in syntaxin transport in neurons. Nat. Cell Biol. 6, 941-953.
34. Vale, R.D., 2003. The molecular motor toolbox for intracellular transport. Cell 112, 467-480.
35. Wu, X., Chen, L., Sui, C., Hu, Y., Jiang, D., Yang, F., Miller, L.C., Li, J., Cong, X., Hrabchenko, N., Lee, C., Du, Y., Qi, J., 2023. 3C(pro) of FMDV inhibits type II interferon-stimulated JAK-STAT signaling pathway by blocking STAT1 nuclear translocation. Virol. Sin. 38, 387-397.
36. Yamazaki, H., Nakata, T., Okada, Y., Hirokawa, N., 1995. Kif3a/B - a heterodimeric kinesin superfamily protein that works as a microtubule plus end-directed motor for membrane organelle transport. J. Cell Biol. 130, 1387-1399.
37. Yang, F., Zhu, Z., Cao, W., Liu, H., Wei, T., Zheng, M., Zhang, K., Jin, Y., He, J., Guo, J., Liu, X., Zheng, H., 2020. Genetic determinants of altered virulence of type O foot-and-mouth disease virus. J. Virol. 94.
38. Yang, P., Yuan, Y., Sun, Y., Lv, B., Du, H., Zhou, Z., Yang, Z., Liu, X., Duan, H., Shen, C., 2023. The host protein CAD regulates the replication of FMDV through the function of pyrimidines' de novo synthesis. J. Virol. 97, e0036923.
39. Zhang, W., Yang, F., Zhu, Z., Yang, Y., Wang, Z., Cao, W., Dang, W., Li, L., Mao, R., Liu, Y., Tian, H., Zhang, K., Liu, X., Ma, J., Zheng, H., 2019. Cellular DNAJA3, a novel VP1-interacting protein, inhibits foot-and-mouth disease virus replication by inducing lysosomal degradation of VP1 and attenuating its antagonistic role in the beta interferon signaling pathway. J. Virol. 93.
40. Zhang, X., Yang, F., Li, K., Cao, W., Ru, Y., Chen, S., Li, S., Liu, X., Zhu, Z., Zheng, H., 2021. The insufficient activation of RIG-I-like signaling pathway contributes to highly efficient replication of porcine picornaviruses in IBRS-2 cells. Mol. Cell. Proteomics 20, 100147.
41. Zhu, P.Y., Ji, W.Q., Li, D., Li, Z.J., Chen, Y., Dai, B.W., Han, S.J., Chen, S.Y., Jin, Y.F., Duan, G.C., 2023. Current status of hand-foot-and-mouth disease. J. Biomed. Sci. 30.
Proportional views