The glycoprotein (G protein) of VSV is responsible for the attachment and entry of VSV into a susceptible host cell and is therefore essential for virus infectivity. To identify and dissect the signals required for the replication and assembly of VSV Dr. Michael Whitt has developed a "reverse genetics" system in which the G protein of VSV has been deleted (rVSV-ΔG). rVSV-ΔG has been used to produce VSV pseudotypes containing the envelope glycoproteins of heterologous viruses including viruses that require high-level containment (e.g., encephalitis viruses, SARS coronavirus, SARS-CoV-2, MERS coronavirus, etc.). Since the infectivity of rVSV-ΔG is restricted to a single round of replication, analyses of viral entry can be performed using just biosafety level 2 (BSL-2) containment.
This Delta-G-VSV Pseudotyping System has proven useful for identifying cellular receptors for viruses, screening for entry inhibitors, and evaluating neutralizing antibody responses following vaccination. Originally described in a 2010 methods article (PMID: 20709108), the system is now used as a virus model system by researchers worldwide. Most recently, the system is being applied to study COVID-19 infection.