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| Critical role of cytochrome c1 and its cleavage in porcine reproductive and respiratory syndrome virus nonstructural protein 4-induced cell apoptosis via interaction with nsp4 |
| ZHANG Feng, GAO Peng, GE Xin-na, ZHOU Lei, GUO Xin, YANG Han-chun |
| Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, P.R.China |
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Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) actively induces cell apoptosis both in vitro and in vivo, which can contribute critically to viral pathogenesis. Previous studies have shown that the PRRSV nonstructural protein 4 (nsp4) is an important mediator of this process, but the underlying molecular details remain poorly understood. In this study, we found that the PRRSV nsp4 interacted with the mitochondrial inner membrane protein cytochrome c1 (cyto.c1) and induced its proteolytic cleavage. Interestingly, the cleaved N-terminal fragment of cyto.c1 was found to exert apoptotic activity, which could cause mitochondrial fragmentation, resulting in apoptotic cell death. And RNA interference (RNAi) silencing experiments further confirmed the crucial role which cyto.c1 played in nsp4- and PRRSV-induced cell apoptosis. Thus, our data provide an important piece of mechanistic clues for PRRSV-induced cell apoptosis and also elucidate a novel mechanism for the 3C-like proteases in this finding.
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Received: 09 March 2017
Accepted:
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| Fund: This study was supported by the National 973 Program of China (2014CB542700), the National Natural Science Foundation of China (31330077, 31540004), and the earmarked fund for China Agriculture Research System (CARS-36). |
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Corresponding Authors:
Correspondence YANG Han-chun, Tel/Fax: +86-10-62731296, E-mail: yanghanchun1@cau.edu.cn
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| About author: ZHANG Feng, Tel: +86-10-62733962, E-mail: xhz-111@163.com |
Cite this article:
ZHANG Feng, GAO Peng, GE Xin-na, ZHOU Lei, GUO Xin, YANG Han-chun.
2017.
Critical role of cytochrome c1 and its cleavage in porcine reproductive and respiratory syndrome virus nonstructural protein 4-induced cell apoptosis via interaction with nsp4. Journal of Integrative Agriculture, 16(11): 2573-2585.
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| Albina E. 1997. Epidemiology of porcine reproductive and respiratory syndrome (PRRS): An overview. Veterinary Microbiology, 55, 309–316.Barco A, Feduchi E, Carrasco L. 2000. Poliovirus protease 3C(pro) kills cells by apoptosis. Virology, 266, 352–360.Cape J L, Bowman M K, Kramer D M. 2007. A semiquinone intermediate generated at the Qo site of the cytochrome bc1 complex: importance for the Q-cycle and superoxide production. Proceedings of the National Academy of Sciences of the United States of America, 104, 7887–7892.Choi C, Chae C. 2002. Expression of tumour necrosis factor-alpha is associated with apoptosis in lungs of pigs experimentally infected with porcine reproductive and respiratory syndrome virus. Research in Veterinary Science, 72, 45–49.Crofts A R. 2004. The cytochrome bc1 complex: Function in the context of structure. Annual Review of Physiology, 66, 689–733.Du J , Ge X, Liu Y , Wang Z, Zhang R, Zhou L, Guo X, Han J, Yang H. 2016. Targeting swine leukocyte antigen class I molecules for proteasomal degradation by the nsp1α replicase protein of the chinese highly pathogenic porcine reproductive and respiratory syndrome virus strain JXwn06. Journal of Virology, 90, 682–693.Feng W H, Tompkins M B, Xu J S, Brown T T, Laster S M, Zhang H X, McCaw M B. 2002. Thymocyte and peripheral blood T lymphocyte subpopulation changes in piglets following in utero infection with porcine reproductive and respiratory syndrome virus. Virology, 302, 363–372.Fernandez A, Suarez P, Castro J M, Tabares E, Diaz-Guerra M. 2002. Characterization of regions in the GP5 protein of porcine reproductive and respiratory syndrome virus required to induce apoptotic cell death. Virus Research, 83, 103–118.Gagnon C A, Lachapelle G, Langelier Y, Massie B, Dea S. 2003. Adenoviral-expressed GP5 of porcine respiratory and reproductive syndrome virus differs in its cellular maturation from the authentic viral protein but maintains known biological functions. Archives of Virology, 148, 951–972.Galluzzi L, Brenner C, Morselli E, Touat Z, Kroemer G. 2008. Viral control of mitochondrial apoptosis. PLoS Pathogens, 4, e1000018.Guo B, Lager K M, Henningson J N, Miller L C, Schlink S N, Kappes M A, Kehrli M E, Brockmeier S L, Nicholson T L, Yang H C, Faaberg K S. 2013. Experimental infection of United States swine with a Chinese highly pathogenic strain of porcine reproductive and respiratory syndrome virus. Virology, 435, 372–384.Han J, Rutherford M S, Faaberg K S. 2009. The porcine reproductive and respiratory syndrome virus nsp2 cysteine protease domain possesses both trans- and cis-cleavage activities. Journal of Virology, 83, 9449–9463.He Y, Wang G, Liu Y, Shi W, Han Z, Wu J, Jiang C, Wang S, Hu S, Wen H, Dong J, Liu H, Cai X. 2012. Characterization of thymus atrophy in piglets infected with highly pathogenic porcine reproductive and respiratory syndrome virus. Veterinary Microbiology, 160, 455–462.Hunte C, Palsdottir H, Trumpower B L. 2003. Protonmotive pathways and mechanisms in the cytochrome bc1 complex. FEBS Letters, 545, 39–46.Kim T S, Benfield D A, Rowland R R. 2002. Porcine reproductive and respiratory syndrome virus-induced cell death exhibits features consistent with a nontypical form of apoptosis. Virus Research, 85, 133–140.Kuhn J H, Lauck M, Bailey A L, Shchetinin A M, Vishnevskaya T V, Bao Y, Ng T F, LeBreton M, Schneider B S, Gillis A, Tamoufe U, Diffo Jle D, Takuo J M, Kondov N O, Coffey L L, Wolfe N D, Delwart E, Clawson A N, Postnikova E, Bollinger L, et al. 2016. Reorganization and expansion of the nidoviral family Arteriviridae. Archives of Virology, 161, 755–768.Labarque G, Van Gucht S, Nauwynck H, Van Reeth K, Pensaert M. 2003. Apoptosis in the lungs of pigs infected with porcine reproductive and respiratory syndrome virus and associations with the production of apoptogenic cytokines. Veterinary Research, 34, 249–260.Lee C, Rogan D, Erickson L, Zhang J, Yoo D. 2004. Characterization of the porcine reproductive and respiratory syndrome virus glycoprotein 5 (GP5) in stably expressing cells. Virus Research, 104, 33–38.Lee S M, Kleiboeker S B. 2007. Porcine reproductive and respiratory syndrome virus induces apoptosis through a mitochondria-mediated pathway. Virology, 365, 419–434.Li L, Zhao Q, Ge X, Teng K, Kuang Y, Chen Y, Guo X, Yang H. 2012. Chinese highly pathogenic porcine reproductive and respiratory syndrome virus exhibits more extensive tissue tropism for pigs. Virology Journal, 9, doi: 10.1186/1743-422X-9-203Li Y, Wang G, Liu Y, Tu Y, He Y, Wang Z, Han Z, Li L, Li A, Tao Y, Cai X. 2014a. Identification of apoptotic cells in the thymus of piglets infected with highly pathogenic porcine reproductive and respiratory syndrome virus. Virus Research, 189, 29–33.Li Y, Zhou L, Zhang J, Ge X, Zhou R, Zheng H, Geng G, Guo X, Yang H. 2014b. Nsp9 and Nsp10 contribute to the fatal virulence of highly pathogenic porcine reproductive and respiratory syndrome virus emerging in China. PLoS Pathogens, 10, e1004216.Lin C W, Lin K H, Hsieh T H, Shiu S Y, Li J Y. 2006. Severe acute respiratory syndrome coronavirus 3C-like protease-induced apoptosis. FEMS Immunology and Medical Microbiology, 46, 375–380.Ma Z, Wang Y, Zhao H, Xu A T, Wang Y, Tang J, Feng W H. 2013. Porcine reproductive and respiratory syndrome virus nonstructural protein 4 induces apoptosis dependent on its 3C-like serine protease activity. PLoS ONE, 8, e69387.Miller L C, Fox J M. 2004. Apoptosis and porcine reproductive and respiratory syndrome virus. Veterinary Immunology and Immunopathology, 102, 131–142.Mu Y, Li L, Zhang B, Huang B, Gao J, Wang X, Wang C, Xiao S, Zhao Q, Sun Y, Zhang G, Hiscox J A, Zhou E M. 2015. Glycoprotein 5 of porcine reproductive and respiratory syndrome virus strain SD16 inhibits viral replication and causes G2/M cell cycle arrest, but does not induce cellular apoptosis in Marc-145 cells. Virology, 484, 136–145.Neumann E J, Kliebenstein J B, Johnson C D, Mabry J W, Bush E J, Seitzinger A H, Green A L, Zimmerman J J. 2005. Assessment of the economic impact of porcine reproductive and respiratory syndrome on swine production in the United States. Journal of the American Veterinary Medical Association, 227, 385–392.Neumann S, El Maadidi S, Faletti L, Haun F, Labib S, Schejtman A, Maurer U, Borner C. 2015. How do viruses control mitochondria-mediated apoptosis? Virus Research, 209, 45–55.O’Brien V. 1998. Viruses and apoptosis. The Journal of General Virology, 79, 1833–1845.Rossow K D. 1998. Porcine reproductive and respiratory syndrome. Veterinary Pathology, 35, 1–20.Roulston A, Marcellus R C, Branton P E. 1999. Viruses and apoptosis. Annual Review of Microbiology, 53, 577–628.Sirinarumitr T, Zhang Y, Kluge J P, Halbur P G, Paul P S. 1998. A pneumo-virulent United States isolate of porcine reproductive and respiratory syndrome virus induces apoptosis in bystander cells both in vitro and in vivo. The Journal of General Virology, 79, 2989–2995.Suarez P, Diaz-Guerra M, Prieto C, Esteban M, Castro J M, Nieto A, Ortin J. 1996. Open reading frame 5 of porcine reproductive and respiratory syndrome virus as a cause of virus-induced apoptosis. Journal of Virology, 70, 2876–2882.Sur J H, Doster A R, Christian J S, Galeota J A, Wills R W, Zimmerman J J, Osorio F A. 1997. Porcine reproductive and respiratory syndrome virus replicates in testicular germ cells, alters spermatogenesis, and induces germ cell death by apoptosis. Journal of Virology, 71, 9170–9179.Sur J H, Doster A R, Osorio F A. 1998. Apoptosis induced in vivo during acute infection by porcine reproductive and respiratory syndrome virus. Veterinary Pathology, 35, 506–514.Teodoro J G, Branton P E. 1997. Regulation of apoptosis by viral gene products. Journal of Virology, 71, 1739–1746.Tian K, Yu X, Zhao T, Feng Y, Cao Z, Wang C, Hu Y, Chen X, Hu D, Tian X, Liu D, Zhang S, Deng X, Ding Y, Yang L, Zhang Y, Xiao H, Qiao M, Wang B, Hou L, et al. 2007. Emergence of fatal PRRSV variants: Unparalleled outbreaks of atypical PRRS in China and molecular dissection of the unique hallmark. PLoS ONE, 2, e526.Tian X, Lu G, Gao F, Peng H, Feng Y, Ma G, Bartlam M, Tian K, Yan J, Hilgenfeld R, Gao G F. 2009. Structure and cleavage specificity of the chymotrypsin-like serine protease (3CLSP/nsp4) of porcine reproductive and respiratory syndrome virus (PRRSV). Journal of Molecular Biology, 392, 977–993.Wang G, He Y, Tu Y, Liu Y, Zhou E M, Han Z, Jiang C, Wang S, Shi W, Cai X. 2014. Comparative analysis of apoptotic changes in peripheral immune organs and lungs following experimental infection of piglets with highly pathogenic and classical porcine reproductive and respiratory syndrome virus. Virology Journal, 11, doi: 10.1186/1743-422X-11-2Wang G, Song T, Yu Y, Liu Y, Shi W, Wang S, Rong F, Dong J, Liu H, Cai X, Zhou E M. 2011. Immune responses in piglets infected with highly pathogenic porcine reproductive and respiratory syndrome virus. Veterinary Immunology and Immunopathology, 142, 170–178.Wang L, He Q, Gao Y, Guo X, Ge X, Zhou L, Yang H. 2012. Interaction of cellular poly(C)-binding protein 2 with nonstructural protein 1beta is beneficial to Chinese highly pathogenic porcine reproductive and respiratory syndrome virus replication. Virus Research, 169, 222–230.Yuan S, Zhang N, Xu L, Zhou L, Ge X, Guo X, Yang H. 2016. Induction of apoptosis by the nonstructural protein 4 and 10 of porcine reproductive and respiratory syndrome virus. PLoS ONE, 11, e0156518.Zaragoza C, Saura M, Padalko E Y, Lopez-Rivera E, Lizarbe T R, Lamas S, Lowenstein C J. 2006. Viral protease cleavage of inhibitor of kappaBalpha triggers host cell apoptosis. Proceedings of the National Academy of Sciences of the United States of America, 103, 19051–19056.Zhang H, Guo X, Ge X, Chen Y, Sun Q, Yang H. 2009. Changes in the cellular proteins of pulmonary alveolar macrophage infected with porcine reproductive and respiratory syndrome virus by proteomics analysis. Journal of Proteome Research, 8, 3091–3097.Zhao K, Ye C, Chang X B, Jiang C G, Wang S J, Cai X H, Tong G Z, Tian Z J, Shi M, An T Q. 2015. Importation and recombination are responsible for the latest emergence of highly pathogenic porcine reproductive and respiratory syndrome virus in China. Journal of Virology, 89, 10712–10716.Zhou L, Wang Z, Ding Y, Ge X, Guo X, Yang H. 2015. NADC30-like strain of porcine reproductive and respiratory syndrome virus, China. Emerging Infectious Diseases, 21, 2256–2257.Zhou L, Yang H. 2010. Porcine reproductive and respiratory syndrome in China. Virus Research, 154, 31–37.Zhou L, Zhang J, Zeng J, Yin S, Li Y, Zheng L, Guo X, Ge X, Yang H. 2009. The 30-amino-acid deletion in the Nsp2 of highly pathogenic porcine reproductive and respiratory syndrome virus emerging in China is not related to its virulence. Journal of Virology, 83, 5156–5167.Zhu Y, Li M, Wang X, Jin H, Liu S, Xu J, Chen Q. 2012. Caspase cleavage of cytochrome c1 disrupts mitochondrial function and enhances cytochrome c release. Cell Research, 22, 127–141.Ziebuhr J, Snijder E J, Gorbalenya A E. 2000. Virus-encoded proteinases and proteolytic processing in the Nidovirales. The Journal of General Virology, 81, 853–879. |
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