title: Novel interactions of domain III from the envelope glycoprotein of dengue 2 virus with human plasma proteins.
abstract: Blood cells and plasma are important media for the four serotypes of dengue virus (DENV1-4) spreading into an infected person. Thus, interactions with human plasma proteins are expected to be decisive in the course of the viral infection. Affinity purification followed by MS analysis (AP/MS) was used to isolate and identify plasma-derived proteins capable to interact with a recombinant protein comprising the domain III of the envelope protein of DENV2 (DIIIE2). The elution of the AP potently inhibits DENV2 infection. Twenty-nine proteins were identified using a label-free approach as specifically captured by DIIIE2. Of these, a direct interaction with C reactive protein, thrombin and Inter-alpha-inhibitor complexes was confirmed by ELISA. Results provide further evidence of a significant representation of proteins from complement and coagulation cascades on DENV2 interactome in human plasma and stand out the domain III of the viral envelope protein as participant on these interactions. A functional clustering analysis highlights the presence of three structural motifs among putative DIIIE2-binding proteins: hydroxylation and EGF-like calcium-binding- and Gla domains.
  
  
  CONCLUSIONS
  Early cycles of dengue virus replication take place in human blood cells. Thus, the characterization of the interactome of dengue virus proteins in human plasma can lead to the identification of pivotal interactions for the infection that can eventually constitute the target for the development of methods to control dengue virus-caused disease. In this work we identified 29 proteins from human plasma that potentially interact with the envelope protein of dengue 2 virus either directly or through co-complex formation. C reactive protein, thrombin and Inter-alpha-inhibitor complexes were validated as interactors of the domain III of the envelope protein of dengue 2. Results highlight the presence of three structural motifs among putative DIIIE2-binding proteins: hydroxylation and EGF-like calcium-binding- and Gla domains. This finding together with the participation of domain III of the envelope protein on the interactions with human plasma proteins should contribute to a better understanding of dengue virus interactome in human plasma. Such knowledge can contribute to the development of more effective treatments to infected persons.
authors.affiliation: Center for Genetic Engineering and Biotechnology, Cuba. Electronic address: vivian.huerta@cigb.edu.cu.
authors.forename: Vivian
authors.initials: V
authors.lastname: Huerta
authors.affiliation: Center for Genetic Engineering and Biotechnology, Cuba.
authors.forename: Yassel
authors.initials: Y
authors.lastname: Ramos
authors.affiliation: Center for Genetic Engineering and Biotechnology, Cuba.
authors.forename: Alexis
authors.initials: A
authors.lastname: Yero
authors.affiliation: Center for Genetic Engineering and Biotechnology, Cuba.
authors.forename: Dianne
authors.initials: D
authors.lastname: Pupo
authors.affiliation: Center for Genetic Engineering and Biotechnology, Cuba.
authors.forename: Dayron
authors.initials: D
authors.lastname: Martín
authors.affiliation: Center for Genetic Engineering and Biotechnology, Cuba.
authors.forename: Patricia
authors.initials: P
authors.lastname: Toledo
authors.affiliation: Center for Genetic Engineering and Biotechnology, Cuba.
authors.forename: Noralvis
authors.initials: N
authors.lastname: Fleitas
authors.affiliation: Luxembourg Clinical Proteomics Center, Luxembourg.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gallien
authors.affiliation: Center for Genetic Engineering and Biotechnology, Cuba.
authors.forename: Alejandro M
authors.initials: AM
authors.lastname: Martín
authors.affiliation: Center for Genetic Engineering and Biotechnology, Cuba.
authors.forename: Gabriel J
authors.initials: GJ
authors.lastname: Márquez
authors.affiliation: Center for Genetic Engineering and Biotechnology, Cuba.
authors.forename: Yasset
authors.initials: Y
authors.lastname: Pérez-Riverol
authors.affiliation: Center for Genetic Engineering and Biotechnology, Cuba.
authors.forename: Mónica
authors.initials: M
authors.lastname: Sarría
authors.affiliation: Center for Genetic Engineering and Biotechnology, Cuba.
authors.forename: Osmany
authors.initials: O
authors.lastname: Guirola
authors.affiliation: Center for Genetic Engineering and Biotechnology, Cuba.
authors.forename: Luis J
authors.initials: LJ
authors.lastname: González
authors.affiliation: Luxembourg Clinical Proteomics Center, Luxembourg.
authors.forename: Bruno
authors.initials: B
authors.lastname: Domon
authors.affiliation: Center for Genetic Engineering and Biotechnology, Cuba.
authors.forename: Glay
authors.initials: G
authors.lastname: Chinea
mesh_terms: D001665:Binding Sites; D001798:Blood Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D001798:Blood Proteins; C051821:E-glycoprotein, Dengue virus type 2; D014759:Viral Envelope Proteins
keywords: Affinity purification; Dengue; Domain III; Plasma; Protein interaction