1887

Abstract

Recently, Zika virus (ZIKV) outbreak has been associated with a sharp increase in cases of Guillain–Barré syndrome and severe fetal abnormalities. However, the mechanism underlying the interaction of ZIKV with host cells is not yet clear. Axl, a receptor tyrosine kinase, is postulated as a receptor for ZIKV entry; however, its in vivo role during ZIKV infection and its impact on the outcome of the disease have not been fully characterized and evaluated. Moreover, there are contradictory results on its involvement in ZIKV infection. Here we utilized Axl-deficient mice (Axl) and their littermates (Axl) to study the in vivo role of Axl in ZIKV infection. Our results showed that both Axl and Axl suckling mice supported the replication of ZIKV and presented clinical manifestations. No significant difference has been found between Axl-deficient mice and their littermates in terms of the survival rate, clinical manifestations, viral load, ZIKV distribution and histopathological changes in major organs. These results therefore indicate that Axl is not an indispensable factor for ZIKV infection in mice.

Keyword(s): Axl , brain , in vivo role , receptor and ZIKV
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2017-08-08
2019-09-18
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References

  1. Du Toit A. Viral infection: Zika virus structure, epidemiology and evolution. Nat Rev Microbiol 2016;14:267 [CrossRef]
    [Google Scholar]
  2. Wang Z, Wang P, An J. Zika virus and Zika fever. Virol Sin 2016;31:103–109 [CrossRef][PubMed]
    [Google Scholar]
  3. Lessler J, Chaisson LH, Kucirka LM, Bi Q, Grantz K et al. Assessing the global threat from Zika virus. Science 2016;353:aaf8160 [CrossRef][PubMed]
    [Google Scholar]
  4. Petersen LR, Jamieson DJ, Powers AM, Honein MA. Zika virus. N Engl J Med 2016;374:1552–1563 [CrossRef][PubMed]
    [Google Scholar]
  5. Cauchemez S, Besnard M, Bompard P, Dub T, Guillemette-Artur P et al. Association between Zika virus and microcephaly in French Polynesia, 2013-15: a retrospective study. Lancet 2016;387:2125–2132 [CrossRef][PubMed]
    [Google Scholar]
  6. Lazear HM, Govero J, Smith AM, Platt DJ, Fernandez E et al. A mouse model of Zika virus pathogenesis. Cell Host Microbe 2016;19:720–730 [CrossRef][PubMed]
    [Google Scholar]
  7. Li C, Xu D, Ye Q, Hong S, Jiang Y et al. Zika virus disrupts neural progenitor development and leads to microcephaly in mice. Cell Stem Cell 2016;19:120–126 [CrossRef][PubMed]
    [Google Scholar]
  8. Mlakar J, Korva M, Tul N, Popović M, Poljšak-Prijatelj M et al. Zika virus associated with microcephaly. N Engl J Med 2016;374:951–958 [CrossRef][PubMed]
    [Google Scholar]
  9. Zhang FC, Li XF, Deng YQ, Tong YG, Qin CF. Excretion of infectious Zika virus in urine. Lancet Infect Dis 2016;16:641–642 [CrossRef][PubMed]
    [Google Scholar]
  10. Govero J, Esakky P, Scheaffer SM, Fernandez E, Drury A et al. Zika virus infection damages the testes in mice. Nature 2016;540:438–442 [CrossRef][PubMed]
    [Google Scholar]
  11. Ma W, Li S, Ma S, Jia L, Zhang F et al. Zika virus causes testis damage and leads to male infertility in mice. Cell 2017;168:542 [CrossRef][PubMed]
    [Google Scholar]
  12. Uraki R, Hwang J, Jurado KA, Householder S, Yockey LJ et al. Zika virus causes testicular atrophy. Sci Adv 2017;3:e1602899 [CrossRef][PubMed]
    [Google Scholar]
  13. Graham DK, Deryckere D, Davies KD, Earp HS. The TAM family: phosphatidylserine sensing receptor tyrosine kinases gone awry in cancer. Nat Rev Cancer 2014;14:769–785 [CrossRef][PubMed]
    [Google Scholar]
  14. Meertens L, Carnec X, Lecoin MP, Ramdasi R, Guivel-Benhassine F et al. The TIM and TAM families of phosphatidylserine receptors mediate dengue virus entry. Cell Host Microbe 2012;12:544–557 [CrossRef][PubMed]
    [Google Scholar]
  15. Nowakowski TJ, Pollen AA, di Lullo E, Sandoval-Espinosa C, Bershteyn M et al. Expression analysis highlights AXL as a candidate Zika virus entry receptor in neural stem cells. Cell Stem Cell 2016;18:591–596 [CrossRef][PubMed]
    [Google Scholar]
  16. Hamel R, Dejarnac O, Wichit S, Ekchariyawat P, Neyret A et al. Biology of Zika virus infection in human skin cells. J Virol 2015;89:8880–8896 [CrossRef][PubMed]
    [Google Scholar]
  17. Savidis G, Mcdougall WM, Meraner P, Perreira JM, Portmann JM et al. Identification of Zika virus and Dengue virus dependency factors using functional genomics. Cell Rep 2016;16:232–246 [CrossRef][PubMed]
    [Google Scholar]
  18. Liu S, Delalio LJ, Isakson BE, Wang TT. AXL-Mediated productive infection of human endothelial cells by Zika virus. Circ Res 2016;119:1183–1189 [CrossRef][PubMed]
    [Google Scholar]
  19. Meertens L, Labeau A, Dejarnac O, Cipriani S, Sinigaglia L et al. Axl mediates ZIKA virus entry in human glial cells and modulates innate immune responses. Cell Rep 2017;18:324–333 [CrossRef][PubMed]
    [Google Scholar]
  20. Miner JJ, Sene A, Richner JM, Smith AM, Santeford A et al. Zika virus infection in mice causes panuveitis with shedding of virus in tears. Cell Rep 2016;16:3208–3218 [CrossRef][PubMed]
    [Google Scholar]
  21. Cugola FR, Fernandes IR, Russo FB, Freitas BC, Dias JL et al. The Brazilian Zika virus strain causes birth defects in experimental models. Nature 2016;534:267–271 [CrossRef][PubMed]
    [Google Scholar]
  22. Herculano-Houzel S, Lent R. Isotropic fractionator: a simple, rapid method for the quantification of total cell and neuron numbers in the brain. J Neurosci 2005;25:2518–2521 [CrossRef][PubMed]
    [Google Scholar]
  23. Jacque CM, Vinner C, Kujas M, Raoul M, Racadot J et al. Determination of glial fibrillary acidic protein (GFAP) in human brain tumors. J Neurol Sci 1978;35:147–155 [CrossRef][PubMed]
    [Google Scholar]
  24. Roessmann U, Velasco ME, Sindely SD, Gambetti P. Glial fibrillary acidic protein (GFAP) in ependymal cells during development. An immunocytochemical study. Brain Res 1980;200:13–21 [CrossRef][PubMed]
    [Google Scholar]
  25. Wells MF, Salick MR, Wiskow O, Ho DJ, Worringer KA et al. Genetic ablation of Axl does not protect human neural progenitor cells and cerebral organoids from Zika virus infection. Cell Stem Cell 2016;19:703–708 [CrossRef][PubMed]
    [Google Scholar]
  26. Hastings AK, Yockey LJ, Jagger BW, Hwang J, Uraki R et al. TAM receptors are not required for Zika virus infection in mice. Cell Rep 2017;19:558–568 [CrossRef][PubMed]
    [Google Scholar]
  27. Li F, Wang PR, Qu LB, Yi CH, Zhang FC et al. Axl is not essential for Zika virus infection in the mouse brain. Emerg Microbes Infect 2017;6:e16 [CrossRef][PubMed]
    [Google Scholar]
  28. Cruz-Oliveira C, Freire JM, Conceição TM, Higa LM, Castanho MA et al. Receptors and routes of dengue virus entry into the host cells. FEMS Microbiol Rev 2015;39:155–170 [CrossRef][PubMed]
    [Google Scholar]
  29. Chen Y, Maguire T, Hileman RE, Fromm JR, Esko JD et al. Dengue virus infectivity depends on envelope protein binding to target cell heparan sulfate. Nat Med 1997;3:866–871 [CrossRef][PubMed]
    [Google Scholar]
  30. Navarro-Sanchez E, Altmeyer R, Amara A, Schwartz O, Fieschi F et al. Dendritic-cell-specific ICAM3-grabbing non-integrin is essential for the productive infection of human dendritic cells by mosquito-cell-derived dengue viruses. EMBO Rep 2003;4:723–728 [CrossRef][PubMed]
    [Google Scholar]
  31. Zhang JL, Wang JL, Gao N, Chen ZT, Tian YP et al. Up-regulated expression of β3 integrin induced by dengue virus serotype 2 infection associated with virus entry into human dermal microvascular endothelial cells. Biochem Biophys Res Commun 2007;356:763–768 [CrossRef][PubMed]
    [Google Scholar]
  32. Li MY, Grandadam M, Kwok K, Lagache T, Siu YL et al. KDEL receptors assist Dengue virus exit from the endoplasmic reticulum. Cell Rep 2015;10:1496–1507 [CrossRef][PubMed]
    [Google Scholar]
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