Abstract
Tetraspanin family of proteins participates in numerous fundamental signaling pathways involved in viral transmission, virus-specific immunity, and virus-mediated vesicular trafficking. Studies in the identification of novel therapeutic candidates and strategies to target West Nile virus, dengue and Zika viruses are highly warranted due to the failure in development of vaccines. Recent evidences have shown that the widely distributed tetraspanin proteins may provide a platform for the development of novel therapeutic approaches. In this review, we discuss the diversified and important functions of tetraspanins in exosome/extracellular vesicle biology, virus-host interactions, virus-mediated vesicular trafficking, modulation of immune mechanism(s), and their possible role(s) in host antiviral defense mechanism(s) through interactions with noncoding RNAs. We also highlight the role of tetraspanins in the development of novel therapeutics to target arthropod-borne flaviviral diseases.
Highlights
Membrane receptor proteins actively participate in order to control specific cellular functions due to their unique architecture, composition, stability and their ability to regulate the signaling from inside out [1, 2]
Silencing of tsp29Fb expression resulted in a substantial reduction in DENV2 loads in cells and significantly decreased export of the viral E-protein and RNA genome in exosomes [6]. These findings demonstrated the importance of arthropod tetraspanins in facilitating DENV2 release, replication, and transmission [6]
Our study suggested that inhibition of arthropod tetraspanin Tsp29Fb or inhibition of extracellular vesicle (EVs) via GW4869 (a cell permeable, selective inhibitor for neutral sphingomyelinase (N-SMase)) are both potential therapeutics to block DENV2/3 and perhaps other mosquito-borne flaviviruses [6]
Summary
Tetraspanin family of proteins participates in numerous fundamental signaling pathways involved in viral transmission, virus-specific immunity, and virus-mediated vesicular trafficking. Studies in the identification of novel therapeutic candidates and strategies to target West Nile virus, dengue and Zika viruses are highly warranted due to the failure in development of vaccines. Recent evidences have shown that the widely distributed tetraspanin proteins may provide a platform for the development of novel therapeutic approaches. We discuss the diversified and important functions of tetraspanins in exosome/extracellular vesicle biology, virus-host interactions, virusmediated vesicular trafficking, modulation of immune mechanism(s), and their possible role(s) in host antiviral defense mechanism(s) through interactions with noncoding RNAs. We highlight the role of tetraspanins in the development of novel therapeutics to target arthropod-borne flaviviral diseases
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