Platelet activation and aggregation response to dengue virus nonstructural protein 1 and domains.
J Thromb Haemost
; 19(10): 2572-2582, 2021 10.
Article
en En
| MEDLINE
| ID: mdl-34160117
ABSTRACT
BACKGROUND:
Platelets are now recognized as immunological sentries in the first line of defense that participate in the detection and response to pathogens. This frequently results in a decrease in the number of circulating platelets. Different mechanisms have been hypothesized to explain the thrombocytopenia in patients with severe dengue, one of them is the participation of the non-structural protein 1 (NS1) of dengue virus (DENV), which can be secreted into circulation during DENV infection and promotes a more efficient infection.OBJECTIVE:
The present study aimed to investigate the ability of platelet response to stimulation with full-length DENV NS1 protein and its domains.METHODS:
DENV NS1 plasmid was transfected into HEK-293T. Proteins were purified by Niquel Sepharose affinity chromatography. Secreted proteins were assessed by sodium dodecylsulfate polyacrylamide gel electrophoresis, Coomassie staining and western blot. Platelet-rich plasma was directly incubated with DENV NS1 proteins. Platelet activation was confirmed by expression of αIIbßIII and P-selectin by flow cytometry. Platelet aggregation was also assessed using DENV NS1 protein and its individual domains as agonists.RESULTS:
DENV NS1 protein and its domains induce P-selectin and αIIbß3 complex expression on platelet surfaces. DENV NS1 induce a stable platelet aggregation after the addition of a minimal dose of adenosine diphosphate (ADP), epinephrine (EPI), or collagen. Interestingly, only EPI could induce the formation of platelet aggregates after incubation with the protein domains of NS1.CONCLUSION:
Our results suggest that the full DENV NS1 protein and also its domains promote platelet recognition, activation, and aggregation.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dengue
/
Virus del Dengue
Límite:
Humans
Idioma:
En
Revista:
J Thromb Haemost
Asunto de la revista:
HEMATOLOGIA
Año:
2021
Tipo del documento:
Article