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Tissue-specific delivery system via AFF-1-coated pseudotyped Vesicular Stomatitis Virus in C. elegans

Viral-based vectors are widely used for fundamental and translational research; however, production of a tissue-specific targeting vector is often a challenging step. Here, we develop a cell type-specific delivery system, based on vesicular stomatitis virus lacking the viral fusion protein (fusogen) and pseudotyped with AFF-1, a C. elegans cell-to-cell bilateral fusogen from the fusexin family. Following injection of AFF-1-coated virus into the C. elegans pseudocoelom that functions as a circulatory system, we observe specific infection of different cells that express EFF-1 or AFF-1 fusogens. EFF-1-expressing epidermal cells are preferentially infected, whereas mononucleated body wall muscles (BWMs) that do not express any fusogen are rarely infected. The epidermal cells infection is abolished when the host cells do not express EFF-1, while ectopic expression of EFF-1 on BWMs induces their abnormal cell-cell fusion, produces paralyzed-dumpy animals and enhances muscle infection by AFF-1-coated viruses. Thus, our data uncover that AFF-1-coated pseudotyped viruses can be retargeted to desired cells in a controlled manner and serve as a cell-specific delivery system in nematodes with potential applications in regenerative processes, therapies such as dendritic reconnection following injuries, and studies of diverse cellular and viral fusogens.