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Incorporation of CD55 into the Zika Viral Envelope Contributes to Its Stability against Human Complement
Authors:Zahra Malekshahi,Sarah Bernklau,Britta Schiela,Iris Koske,Zoltan Banki,Karin Stiasny,Claire L. Harris,Reinhard Wü  rzner,Heribert Stoiber
Affiliation:1.Institute of Virology, Medical University of Innsbruck, 6020 Innsbruck, Austria; (Z.M.); (S.B.); (B.S.); (I.K.); (Z.B.);2.Center for Virology, Medical University of Vienna, 1090 Vienna, Austria;3.Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE1 7RU, UK;4.Institute of Hygiene & Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria
Abstract:The rapid spread of the virus in Latin America and the association of the infection with microcephaly in newborns or Guillain–Barré Syndrome in adults prompted the WHO to declare the Zika virus (ZIKV) epidemic to be an international public health emergency in 2016. As the virus was first discovered in monkeys and is spread not only by mosquitos but also from human to human, we investigated the stability to the human complement of ZIKV derived from mosquito (ZIKVInsect), monkey (ZIKVVero), or human cells (ZIKVA549 and ZIKVFibro), respectively. At a low serum concentration (10%), which refers to complement concentrations found on mucosal surfaces, the virus was relatively stable at 37 °C. At higher complement levels (up to 50% serum concentration), ZIKV titers differed significantly depending on the cell line used for the propagation of the virus. While the viral titer of ZIKVInsect decreased about two orders in magnitude, when incubated with human serum, the virus derived from human cells was more resistant to complement-mediated lysis (CML). By virus-capture assay and Western blots, the complement regulator protein CD55 was identified to be incorporated into the viral envelope. Blocking of CD55 by neutralizing Abs significantly increased the sensitivity to human complement. Taken together, these data indicate that the incorporation of CD55 from human cells contributes to the stability of ZIKV against complement-mediated virolysis.
Keywords:Zika virus   complement   virolysis   CD55
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