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      Receptor-activated human α2-macroglobulin interacts with the envelope protein of dengue virus and protects virions from temperature-induced inactivation through multivalent binding.

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          Abstract

          Based on the hypothesis that interactions between virions and serum components may influence the outcome of dengue virus (DENV) infections, we decided to use affinity chromatography with domain III from the envelope (E) protein of DENV2 (DIIIE2) as a ligand to isolate virus-binding proteins from human plasma. This approach yielded serum amyloid P (SAP) and α2-macroglobulin (α2M) as novel viral interactors. After confirming the specific binding of both SAP and α2M to DIIIE2 by ELISA, the latter interaction was examined in greater detail. We obtain evidence suggesting that the binding species was actually the receptor-activated form of α2M (α2M*), that α2M* could bind monovalently to recombinant domain III from all four DENV serotypes with affinities in the micromolar range ranking as DENV4>DENV1~DENV2>DENV3 and that this interaction exhibited a strong avidity effect when multivalent binding was favoured (KD 8 × 10(-8) M for DIIIE2). We also showed that α2M* bound to DENV virions of the four serotypes, protecting the virus from temperature-induced inactivation in the absence of serum and enhancing infectivity. The latter effect exhibited an ED50 of 2.9 × 10(-8) M, also suggesting an avidity effect due to multivalent binding. These results will further contribute to the characterization of the virus-host factor interaction network during human DENV infection.

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          Author and article information

          Journal
          J. Gen. Virol.
          The Journal of general virology
          Microbiology Society
          1465-2099
          0022-1317
          Dec 2014
          : 95
          : Pt 12
          Affiliations
          [1 ] Center for Genetic Engineering and Biotechnology (CIGB), PO Box 6162, Havana 10600, Cuba Vivian.huerta@cigb.edu.cu.
          [2 ] Center for Genetic Engineering and Biotechnology (CIGB), PO Box 6162, Havana 10600, Cuba.
          Article
          vir.0.068544-0
          10.1099/vir.0.068544-0
          25100798
          2fa26334-4a24-472d-a0c2-036b13b07025
          History

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