VSV (Vesicular stomatitis virus) is an enveloped, negative-stranded RNA virus with a simple structure. Its ability to infect a wide range of mammalian cell types has made VSV a valuable tool to study virus entry, replication, and assembly. The glycoprotein of VSV (termed VSV-G), which binds to the LDL-receptor (low-density lipoprotein receptor), is responsible for the attachment and entry of VSV into a susceptible host cell.
The VSV-G glycoprotein can be deleted from the VSV (VSV Delta G or VSV ΔG) and replaced with recombinant envelope proteins from a wide variety of viruses, allowing for the generation of pseudotypes that represent robust models to screen for neutralizing antibodies and other inhibitors of virus entry. A VSV Delta G pseudovirus can be engineered to transduce a reporter gene encoding Firefly Luciferase or Fluorescent proteins, so that viral entry can be monitored using luminescence or fluorescence, respectively.
The bald VSV Delta G particles do not contain an envelope glycoprotein and cannot infect cells. They are used as a negative control for transduction.
The Spike Pseudotyped VSV Delta G viral particles contain the trimeric SARS-CoV-2 Spike protein as the envelope protein, and, like SARS-CoV-2, can bind to and infect ACE2-expressing cells.
Advantages of the VSV Delta G model:
- Undergoes only one round of replication; therefore, it is safe to use and requires only a biosafety level 2 (BSL-2) facility
- Can be pseudotyped with a variety of viral envelope glycoproteins
- Represents a robust model of viral infection
- High titer
- Infection and viral entry monitored by transduction of luciferase or fluorescent proteins
- SARS-CoV-2 Spike VSV Delta G is the preferred pseudovirus for infection of Vero-6 and Calu-3 cells