New area for exosome research shows potential therapeutic strategy for treating Dengue Fever.
Despite intensive research, there has been no effective pharmaceutical treatment for Dengue fever. Personal protection measure to avoid mosquito bites and environmental management to prevent mosquito breeding remain the only available strategies to prevent transmission.
In the latest Nature Communications, Dr. Edmond Hsieh’s research team reported their newest findings in treating Dengue fever. This study not only provided a possible therapeutic strategy to treat Dengue fever, but also opened a new avenue for exosomes research field.
Dr. Hsieh’s team found that Dengue viral infection causes extensive haemorrhage and triggers immune-mediated cytokine reaction. The patient’s immune system becomes out of control and difficulties in treatment. They also found that a C-Type lectin receptor (CLEC5A) on macrophages, is a key factor for Dengue infection. They further generated specific antibody to against CLEC5A and successfully increased the survival rate of Dengue infected mice from zero to 50 per cent. However, no matter how hard they modified the antibody, the effectiveness of the treatment still could not break the 50 per cent mark. Dr. Hsieh decided to investigate further, the first author of this paper, Song Pei-Shan, a Ph.D. student at Yang Ming University found that the dengue virus upon infection will cause cytokine reactions that acts through CLEC5A on macrophages and activating platelets.
In this study, the team discovered that dengue virus can activate platelets to induce release of tiny substances, called “extracellular vesicles (EVs)”, or, exosomes. Because these vesicles are so tiny, traditionally they are considered insignificant.
It turned out that exosomes secreted from platelets after dengue viral intrusion are target specific. These vesicles would turn around to target the white blood cells. The attack is precisely targeted toward CLEC5A and TLR2 on both neutrophils and macrophages. This will activate the immune system and cause a cytokine reaction stirred up by the macrophages, the platelet-secreted exosomes targeted neutrophils would release its own DNA to form Neutrophil Extracellular Traps (NETs) this can result in damage on the internal organs.
By treating the dengue viral infected mice with antibodies against CLEC5A and TLR2, the survival rate reached over 90 per cent.
Dr. Hsieh confidently said that this study found not only the critical infection pathway of dengue virus, but also unveiled a previously unknown function of EVs. [APBN]