Proteomic analysis of monkey kidney LLC-MK2 cells infected with a Thai strain Zika virus
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.
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.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Human and animal rights statement
Neither animal nor human testing was involved in this study.
- 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 CrossRefGoogle 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 CrossRefGoogle 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 CrossRefGoogle 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 CrossRefGoogle 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 CrossRefGoogle 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 CrossRefGoogle 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 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 CrossRefGoogle 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 CrossRefGoogle 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 CrossRefGoogle 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 CrossRefGoogle 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 CrossRefGoogle 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 CrossRefGoogle 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 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 CrossRefGoogle 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 CrossRefGoogle 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 CrossRefGoogle 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 CrossRefGoogle 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 CrossRefGoogle Scholar