TY - JOUR
T1 - Novel interactions of domain III from the envelope glycoprotein of dengue 2 virus with human plasma proteins
AU - Huerta, Vivian
AU - Ramos, Yassel
AU - Yero, Alexis
AU - Pupo, Dianne
AU - Martín, Dayron
AU - Toledo, Patricia
AU - Fleitas, Noralvis
AU - Gallien, Sebastien
AU - Martín, Alejandro M.
AU - Márquez, Gabriel J.
AU - Pérez-Riverol, Yasset
AU - Sarría, Mónica
AU - Guirola, Osmany
AU - González, Luis J.
AU - Domon, Bruno
AU - Chinea, Glay
N1 - Funding Information:
This work was supported by The Center for Genetic Engineering and Biotechnology, La Habana, Cuba and PEARL and CORE (Lux-hPDQ and PORT-HPP) grants from the Fonds National de la Recherche Luxembourg (FNR) .
Publisher Copyright:
© 2015 Published by Elsevier B.V.
PY - 2016/1/10
Y1 - 2016/1/10
N2 - 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. Biological significance: 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.
AB - 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. Biological significance: 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.
KW - Affinity purification
KW - Dengue
KW - Domain III
KW - Plasma
KW - Protein interaction
UR - http://www.scopus.com/inward/record.url?scp=84948747993&partnerID=8YFLogxK
U2 - 10.1016/j.jprot.2015.11.003
DO - 10.1016/j.jprot.2015.11.003
M3 - Article
C2 - 26546555
AN - SCOPUS:84948747993
SN - 1874-3919
VL - 131
SP - 205
EP - 213
JO - Journal of Proteomics
JF - Journal of Proteomics
ER -