Secreted complement regulatory protein clusterin interacts with dengue virus nonstructural protein 1

Area of Science:

• Virology
• Immunology
• Biochemistry

Background:

• Vascular leakage and shock are primary causes of mortality in Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS).
• Elevated levels of soluble dengue virus nonstructural protein 1 (sNS1) are linked to increased DHF risk.

Purpose of the Study:

• To identify host molecules in human plasma that interact with dengue virus NS1.
• To elucidate the potential role of NS1-host interactions in the pathogenesis of DHF.

Main Methods:

• Affinity purification using a GST-fused NS1 protein to isolate interacting host molecules from human plasma.
• Mass spectrometry to identify the purified host protein.
• In vitro interaction assays using recombinant sNS1 and sNS1 from infected cells with the identified host protein.

Main Results:

• Clusterin (Clu), a complement inhibitory factor, was identified as a host molecule interacting with NS1.
• Both recombinant sNS1 and sNS1 from infected cells demonstrated interaction with human Clu.
• Clusterin naturally inhibits the formation of the terminal complement complex (TCC).

Conclusions:

• The interaction between dengue virus sNS1 and the complement inhibitor clusterin (Clu) was identified.
• This interaction may contribute to the progression of DHF by potentially affecting complement-mediated vascular leakage.