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Proteomic analysis of monkey kidney LLC-MK2 cells infected with a Thai strain Zika virus

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Abstract

Zika virus (ZIKV) has been endemic in Southeast Asian countries for several years, but the presence of the virus has not been associated with significant outbreaks of infection unlike other countries around the world where the Asian lineage ZIKV was introduced recently. However, few studies have been undertaken using the endemic virus. The Thai isolate was shown to have a similar tissue tropism to an African isolate of ZIKV, albeit that the Thai isolate infected cells at a lower level as compared to the African isolate. To further understand the pathogenesis of the Thai isolate, a 2D-gel proteomic analysis was undertaken of ZIKV infected LLC-MK2 cells. Seven proteins (superoxide dismutase [Mn], peroxiredoxin 2, ATP synthase subunit alpha, annexin A5 and annexin A1, carnitine o-palmitoyltransferase 2 and cytoskeleton-associated protein 2) were identified as differentially regulated. Of four proteins selected for validation, three (superoxide dismutase [Mn], peroxiredoxin 2, ATP synthase subunit alpha, and annexin A1) were shown to be differentially regulated at both the transcriptional and translational levels. The proteins identified were primarily involved in energy production both directly, and indirectly through mediation of autophagy, as well as in the response to oxidative stress, possibly occurring as a consequence of increased energy production. This study provides further new information on the pathogenesis of ZIKV.

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References

  1. Musso D, Gubler DJ (2016) Zika virus. Clin Microbiol Rev 29(3):487–524. https://doi.org/10.1128/CMR.00072-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Faye O, Freire CCM, Iamarino A, Faye O, de Oliveira JVC, Diallo M, Zanotto PMA, Sall AA (2014) Molecular evolution of Zika virus during its emergence in the 20(th) century. PLoS Negl Trop Dis 8(1):e2636. https://doi.org/10.1371/journal.pntd.0002636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Dick GW, Kitchen SF, Haddow AJ (1952) Zika virus. I. Isolations and serological specificity. Trans R Soc Trop Med Hyg 46(5):509–520

    Article  CAS  PubMed  Google Scholar 

  4. Simpson DI (1964) Zika Virus Infection in Man. Trans R Soc Trop Med Hyg 58:335–338

    Article  CAS  PubMed  Google Scholar 

  5. Wikan N, Smith DR (2017) First published report of Zika virus infection in people: Simpson, not MacNamara. Lancet Infect Dis 17(1):15–17. https://doi.org/10.1016/s1473-3099(16)30525-4

    Article  PubMed  Google Scholar 

  6. Wikan N, Smith DR (2016) Zika virus: history of a newly emerging arbovirus. Lancet Infect Dis 16(7):E119–E126. https://doi.org/10.1016/s1473-3099(16)30010-x

    Article  PubMed  Google Scholar 

  7. Lanciotti RS, Kosoy OL, Laven JJ, Velez JO, Lambert AJ, Johnson AJ, Stanfield SM, Duffy MR (2008) Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia. Emerg Infect Dis 14(8):1232–1239. https://doi.org/10.3201/eid1408.080287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Cao-Lormeau VM, Roche C, Teissier A, Robin E, Berry AL, Mallet HP, Sall AA, Musso D (2014) Zika virus, French polynesia, South pacific. Emerg Infect Dis 20(6):1085–1086. https://doi.org/10.3201/eid2006.140138

    Article  PubMed  PubMed Central  Google Scholar 

  9. Campos GS, Bandeira AC, Sardi SI (2015) Zika virus outbreak, Bahia, Brazil. Emerg Infect Dis 21(10):1885–1886. https://doi.org/10.3201/eid2110.150847

    Article  PubMed  PubMed Central  Google Scholar 

  10. Zanluca C, Melo VC, Mosimann AL, Santos GI, Santos CN, Luz K (2015) First report of autochthonous transmission of Zika virus in Brazil. Mem Inst Oswaldo Cruz 110(4):569–572. https://doi.org/10.1590/0074-02760150192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Baud D, Gubler DJ, Schaub B, Lanteri MC, Musso D (2017) An update on Zika virus infection. Lancet 390(10107):2099–2109. https://doi.org/10.1016/S0140-6736(17)31450-2

    Article  PubMed  Google Scholar 

  12. Acosta-Ampudia Y, Monsalve DM, Castillo-Medina LF, Rodriguez Y, Pacheco Y, Halstead S, Willison HJ, Anaya JM, Ramirez-Santana C (2018) Autoimmune neurological conditions associated with Zika virus infection. Front Mol Neurosci 11:116. https://doi.org/10.3389/fnmol.2018.00116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Soriano-Arandes A, Rivero-Calle I, Nastouli E, Espiau M, Frick MA, Alarcon A, Martinon-Torres F (2018) What we know and what we don’t know about perinatal Zika virus infection: a systematic review. Expert Rev Anti Infect Ther 16(3):243–254. https://doi.org/10.1080/14787210.2018.1438265

    Article  CAS  PubMed  Google Scholar 

  14. Khongwichit S, Wikan N, Auewarakul P, Smith DR (2018) Zika virus in Thailand. Microbes Infect 56:6. https://doi.org/10.1016/j.micinf.2018.01.007

    Article  Google Scholar 

  15. Luo H, Winkelmann ER, Fernandez-Salas I, Li L, Mayer SV, Danis-Lozano R, Sanchez-Casas RM, Vasilakis N, Tesh R, Barrett AD, Weaver SC, Wang T (2018) Zika, dengue and yellow fever viruses induce differential anti-viral immune responses in human monocytic and first trimester trophoblast cells. Antiviral Res 151:55–62. https://doi.org/10.1016/j.antiviral.2018.01.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sheridan MA, Balaraman V, Schust DJ, Ezashi T, Roberts RM, Franz AWE (2018) African and Asian strains of Zika virus differ in their ability to infect and lyse primitive human placental trophoblast. PLoS One 13(7):e0200086. https://doi.org/10.1371/journal.pone.0200086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Yuan L, Huang XY, Liu ZY, Zhang F, Zhu XL, Yu JY, Ji X, Xu YP, Li G, Li C, Wang HJ, Deng YQ, Wu M, Cheng ML, Ye Q, Xie DY, Li XF, Wang X, Shi W, Hu B, Shi PY, Xu Z, Qin CF (2017) A single mutation in the prM protein of Zika virus contributes to fetal microcephaly. Science (New York, NY) 358(6365):933–936. https://doi.org/10.1126/science.aam7120

    Article  CAS  Google Scholar 

  18. Leecharoenkiat A, Wannatung T, Lithanatudom P, Svasti S, Fucharoen S, Chokchaichamnankit D, Srisomsap C, Smith DR (2011) Increased oxidative metabolism is associated with erythroid precursor expansion in beta0-thalassaemia/Hb E disease. Blood Cells Mol Dis 47(3):143–157. https://doi.org/10.1016/j.bcmd.2011.06.005

    Article  CAS  PubMed  Google Scholar 

  19. Buathong R, Hermann L, Thaisomboonsuk B, Rutvisuttinunt W, Klungthong C, Chinnawirotpisan P, Manasatienkij W, Nisalak A, Fernandez S, Yoon IK, Akrasewi P, Plipat T (2015) Detection of Zika virus infection in Thailand, 2012–2014. Am J Trop Med Hyg 93(2):380–383. https://doi.org/10.4269/ajtmh.15-0022

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wikan N, Smith DR (2017) Zika virus from a Southeast Asian perspective. Asian Pac J Trop Med 10(1):1–5. https://doi.org/10.1016/j.apjtm.2016.11.013

    Article  PubMed  Google Scholar 

  21. Pond WL (1963) Arthropod-borne virus antibodies in sera from residents of South-East Asia. Trans R Soc Trop Med Hyg 57:364–371

    Article  CAS  PubMed  Google Scholar 

  22. Nitatpattana N, Chaiyo K, Rajakam S, Poolam K, Chansiprasert K, Pesirikan N, Buree S, Rodpai E, Yoksan S (2018) Complete Genome Sequence of a Zika Virus Strain Isolated from the Serum of an Infected Patient in Thailand in 2006. Genome Announc 6:10. https://doi.org/10.1128/genomea.00121-18

    Article  Google Scholar 

  23. Priyamvada L, Hudson W, Ahmed R, Wrammert J (2017) Humoral cross-reactivity between Zika and dengue viruses: implications for protection and pathology. Emerg Microbes Infect 6(5):e33. https://doi.org/10.1038/emi.2017.42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Montoya M, Collins M, Dejnirattisai W, Katzelnick LC, Puerta-Guardo H, Jadi R, Schildhauer S, Supasa P, Vasanawathana S, Malasit P, Mongkolsapaya J, de Silva AD, Tissera H, Balmaseda A, Screaton G, de Silva AM, Harris E (2018) Longitudinal analysis of antibody cross-neutralization following Zika and Dengue virus infection in Asia and the Americas. J Infect Dis. https://doi.org/10.1093/infdis/jiy164

    Article  PubMed  PubMed Central  Google Scholar 

  25. Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucl Acids Res 25(17):3389–3402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Bingham AM, Cone M, Mock V, Heberlein-Larson L, Stanek D, Blackmore C, Likos A (2016) A (2016) comparison of test results for Zika virus RNA in urine, serum, and saliva specimens from persons with travel-associated Zika virus disease—Florida. MMWR Morb Mortal Wkly Rep 65(18):475–478. https://doi.org/10.15585/mmwr.mm6518e2

    Article  PubMed  Google Scholar 

  27. Campos Rde M, Cirne-Santos C, Meira GL, Santos LL, de Meneses MD, Friedrich J, Jansen S, Ribeiro MS, da Cruz IC, Schmidt-Chanasit J, Ferreira DF (2016) Prolonged detection of Zika virus RNA in urine samples during the ongoing Zika virus epidemic in Brazil. J Clin Virol 77:69–70. https://doi.org/10.1016/j.jcv.2016.02.009

    Article  PubMed  Google Scholar 

  28. Chen J, Yang YF, Chen J, Zhou X, Dong Z, Chen T, Yang Y, Zou P, Jiang B, Hu Y, Lu L, Zhang X, Liu J, Xu J, Zhu T (2017) Zika virus infects renal proximal tubular epithelial cells with prolonged persistency and cytopathic effects. Emerg Microbes Infect 6(8):e77. https://doi.org/10.1038/emi.2017.67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Qiu GH, Xie X, Xu F, Shi X, Wang Y, Deng L (2015) Distinctive pharmacological differences between liver cancer cell lines HepG2 and Hep3B. Cytotechnology 67(1):1–12. https://doi.org/10.1007/s10616-014-9761-9

    Article  CAS  PubMed  Google Scholar 

  30. Ghouzzi VE, Bianchi FT, Molineris I, Mounce BC, Berto GE, Rak M, Lebon S, Aubry L, Tocco C, Gai M, Chiotto AM, Sgro F, Pallavicini G, Simon-Loriere E, Passemard S, Vignuzzi M, Gressens P, Di Cunto F (2016) ZIKA virus elicits P53 activation and genotoxic stress in human neural progenitors similar to mutations involved in severe forms of genetic microcephaly. Cell Death Dis 7(10):e2440. https://doi.org/10.1038/cddis.2016.266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Garcez PP, Nascimento JM, de Vasconcelos JM, Madeiro da Costa R, Delvecchio R, Trindade P, Loiola EC, Higa LM, Cassoli JS, Vitoria G, Sequeira PC, Sochacki J, Aguiar RS, Fuzii HT, de Filippis AM (2017) Zika virus disrupts molecular fingerprinting of human neurospheres. Sci Rep 7:40780. https://doi.org/10.1038/srep40780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Jiang X, Dong X, Li SH, Zhou YP, Rayner S, Xia HM, Gao GF, Yuan H, Tang YP, Luo MH (2018) Proteomic analysis of Zika virus infected primary human fetal neural progenitors suggests a role for Doublecortin in the pathological consequences of infection in the Cortex. Front Microbiol 9:1067. https://doi.org/10.3389/fmicb.2018.01067

    Article  PubMed  PubMed Central  Google Scholar 

  33. Coyaud E, Ranadheera C, Cheng DT, Goncalves J, Dyakov B, Laurent E, St-Germain JR, Pelletier L, Gingras AC, Brumell JH, Kim PK, Safronetz D, Raught B (2018) Global interactomics uncovers extensive organellar targeting by Zika virus. Mol Cell Proteom. https://doi.org/10.1074/mcp.tir118.000800

    Article  Google Scholar 

  34. Scaturro P, Stukalov A, Haas DA, Cortese M, Draganova K, Plaszczyca A, Bartenschlager R, Gotz M, Pichlmair A (2018) An orthogonal proteomic survey uncovers novel Zika virus host factors. Nature 561(7722):253–257. https://doi.org/10.1038/s41586-018-0484-5

    Article  CAS  PubMed  Google Scholar 

  35. Johnson F, Giulivi C (2005) Superoxide dismutases and their impact upon human health. Mol Aspects Med 26(4–5):340–352. https://doi.org/10.1016/j.mam.2005.07.006

    Article  CAS  PubMed  Google Scholar 

  36. Olagnier D, Peri S, Steel C, van Montfoort N, Chiang C, Beljanski V, Slifker M, He Z, Nichols CN, Lin R, Balachandran S, Hiscott J (2014) Cellular oxidative stress response controls the antiviral and apoptotic programs in dengue virus-infected dendritic cells. PLoS Pathog 10(12):e1004566. https://doi.org/10.1371/journal.ppat.1004566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Heaton NS, Randall G (2011) Dengue virus and autophagy. Viruses 3(8):1332–1341. https://doi.org/10.3390/v3081332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Cao B, Parnell LA, Diamond MS, Mysorekar IU (2017) Inhibition of autophagy limits vertical transmission of Zika virus in pregnant mice. J Exp Med 214(8):2303–2313. https://doi.org/10.1084/jem.20170957

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Liang Q, Luo Z, Zeng J, Chen W, Foo SS, Lee SA, Ge J, Wang S, Goldman SA, Zlokovic BV, Zhao Z, Jung JU (2016) Zika virus NS4A and NS4B proteins deregulate Akt-mTOR signaling in human fetal neural stem cells to inhibit neurogenesis and induce autophagy. Cell Stem Cell 19(5):663–671. https://doi.org/10.1016/j.stem.2016.07.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Peng H, Liu B, Yves TD, He Y, Wang S, Tang H, Ren H, Zhao P, Qi Z, Qin Z (2018) Zika virus induces autophagy in human umbilical vein endothelial cells. Viruses. https://doi.org/10.3390/v10050259

    Article  PubMed  PubMed Central  Google Scholar 

  41. Kuehnl A, Musiol A, Raabe CA, Rescher U (2016) Emerging functions as host cell factors—an encyclopedia of annexin-pathogen interactions. Biol Chem 397(10):949–959. https://doi.org/10.1515/hsz-2016-0183

    Article  CAS  PubMed  Google Scholar 

  42. Arora S, Lim W, Bist P, Perumalsamy R, Lukman HM, Li F, Welker LB, Yan B, Sethi G, Tambyah PA, Fairhurst AM, Alonso S, Lim LH (2016) Influenza A virus enhances its propagation through the modulation of Annexin-A1 dependent endosomal trafficking and apoptosis. Cell Death Differ 23(7):1243–1256. https://doi.org/10.1038/cdd.2016.19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hiramoto H, Dansako H, Takeda M, Satoh S, Wakita T, Ikeda M, Kato N (2015) Annexin A1 negatively regulates viral RNA replication of hepatitis C virus. Acta Med Okayama 69(2):71–78. https://doi.org/10.18926/AMO/53335

    Article  CAS  PubMed  Google Scholar 

  44. Ghislat G, Aguado C, Knecht E (2012) Annexin A5 stimulates autophagy and inhibits endocytosis. J Cell Sci 125(Pt 1):92–107. https://doi.org/10.1242/jcs.086728

    Article  CAS  PubMed  Google Scholar 

  45. Rufer AC, Thoma R, Hennig M (2009) Structural insight into function and regulation of carnitine palmitoyltransferase. Cell Mol Life Sci 66(15):2489–2501. https://doi.org/10.1007/s00018-009-0035-1

    Article  CAS  PubMed  Google Scholar 

  46. Boyer PD (1997) The ATP synthase–a splendid molecular machine. Annu Rev Biochem 66:717–749. https://doi.org/10.1146/annurev.biochem.66.1.717

    Article  CAS  PubMed  Google Scholar 

  47. Babiychuk EB, Atanassoff AP, Monastyrskaya K, Brandenberger C, Studer D, Allemann C, Draeger A (2011) The targeting of plasmalemmal ceramide to mitochondria during apoptosis. PLoS One 6(8):e23706. https://doi.org/10.1371/journal.pone.0023706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Sun J, Bird CH, Salem HH, Bird P (1993) Association of annexin V with mitochondria. FEBS Lett 329(1–2):79–83

    Article  CAS  PubMed  Google Scholar 

  49. Holley AK, Bakthavatchalu V, Velez-Roman JM, St Clair DK (2011) Manganese superoxide dismutase: guardian of the powerhouse. Int J Mol Sci 12(10):7114–7162. https://doi.org/10.3390/ijms12107114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Barbier V, Lang D, Valois S, Rothman AL, Medin CL (2017) Dengue virus induces mitochondrial elongation through impairment of Drp1-triggered mitochondrial fission. Virology 500:149–160. https://doi.org/10.1016/j.virol.2016.10.022

    Article  CAS  PubMed  Google Scholar 

  51. Chatel-Chaix L, Cortese M, Romero-Brey I, Bender S, Neufeldt CJ, Fischl W, Scaturro P, Schieber N, Schwab Y, Fischer B, Ruggieri A, Bartenschlager R (2016) Dengue virus perturbs mitochondrial morphodynamics to dampen innate immune responses. Cell Host Microbe 20(3):342–356. https://doi.org/10.1016/j.chom.2016.07.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Yu CY, Chang TH, Liang JJ, Chiang RL, Lee YL, Liao CL, Lin YL (2012) Dengue virus targets the adaptor protein MITA to subvert host innate immunity. PLoS Pathog 8(6):e1002780. https://doi.org/10.1371/journal.ppat.1002780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Yu CY, Liang JJ, Li JK, Lee YL, Chang BL, Su CI, Huang WJ, Lai MM, Lin YL (2015) Dengue virus impairs mitochondrial fusion by cleaving mitofusins. PLoS Pathog 11(12):e1005350. https://doi.org/10.1371/journal.ppat.1005350

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Jitobaom K, Tongluan N, Smith DR (2016) Involvement of voltage-dependent anion channel (VDAC) in dengue infection. Sci Rep 6:12. https://doi.org/10.1038/srep35753

    Article  CAS  Google Scholar 

  55. Liu Y, Liu J, Du S, Shan C, Nie K, Zhang R, Li XF, Zhang R, Wang T, Qin CF, Wang P, Shi PY, Cheng G (2017) Evolutionary enhancement of Zika virus infectivity in Aedes aegypti mosquitoes. Nature 545(7655):482–486. https://doi.org/10.1038/nature22365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Pompon J, Morales-Vargas R, Manuel M, Huat Tan C, Vial T, Hao Tan J, Sessions OM, Vasconcelos PDC, Ng LC, Misse D (2017) A Zika virus from America is more efficiently transmitted than an Asian virus by Aedes aegypti mosquitoes from Asia. Sci Rep 7(1):1215. https://doi.org/10.1038/s41598-017-01282-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This work was supported by the Thailand Research Fund (BRG6080006). TD was supported by a scholarship from the Development and Promotion of Science and Technology (DPST) talents project.

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Authors and Affiliations

  1. Molecular Pathology Laboratory, Institute of Molecular Biosciences, Mahidol University, Salaya Campus, 25/25 Phuttamonton Sai 4, Salaya, Nakorn Pathom, 73170, Thailand

    Thamonwan Diteepeng, Sarawut Khongwichit, Atchara Paemanee & Duncan R. Smith

  2. National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Thailand Science Park, Phahonyothin Road, Khlong Nueng, Khlong Luang, Pathum Thani, 12120, Thailand

    Sittiruk Roytrakul

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  1. Thamonwan Diteepeng
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Diteepeng, T., Khongwichit, S., Paemanee, A. et al. Proteomic analysis of monkey kidney LLC-MK2 cells infected with a Thai strain Zika virus. Arch Virol 164, 725–737 (2019). https://doi.org/10.1007/s00705-018-04137-1

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