Pseudotyped Viruses
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Pseudotyping is the process of producing viruses or
viral vector Viral vectors are tools commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism (''in vivo'') or in cell culture (''in vitro''). Viruses have evolved specialized molecul ...
s in combination with foreign viral envelope proteins. The result is a pseudotyped virus particle, also called a pseudovirus. With this method, the foreign viral envelope proteins can be used to alter host tropism or increase or decrease the stability of the virus particles. Pseudotyped particles do not carry the genetic material to produce additional viral envelope proteins, so the phenotypic changes cannot be passed on to progeny viral particles. In some cases, the inability to produce viral envelope proteins renders the pseudovirus replication incompetent. In this way, the properties of dangerous viruses can be studied in a lower risk setting. Pseudotyping allows one to control the expression of envelope proteins. A frequently used protein is the glycoprotein G (VSV-G) from the
Vesicular stomatitis virus ''Indiana vesiculovirus'', formerly ''Vesicular stomatitis Indiana virus'' (VSIV or VSV) is a virus in the family ''Rhabdoviridae''; the well-known ''Rabies lyssavirus'' belongs to the same family. VSIV can infect insects, cattle, horses and pigs ...
(VSV) which mediates entry via the
LDL receptor The low-density lipoprotein receptor (LDL-R) is a mosaic protein of 839 amino acids (after removal of 21-amino acid signal peptide) that mediates the endocytosis of cholesterol-rich low-density lipoprotein (LDL). It is a cell-surface receptor ...
. Envelope proteins incorporated into the pseudovirus allow the virus to readily enter different cell types with the corresponding host
receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...
.


Vaccine development

Pseudotyped virus can be used to vaccinate animals against proteins expressed on the envelope of the virion. This approach has been used to produce vaccine candidates against HIV, ''Nipah henipavirus'', '' Rabies lyssavirus'',
SARS-CoV Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1; or Severe acute respiratory syndrome coronavirus, SARS-CoV) is a strain of coronavirus that causes severe acute respiratory syndrome (SARS), the respiratory illness responsible for t ...
, '' Zaire ebolavirus,'' and SARS-CoV-2. Recombinant vesicular stomatitis virus–Zaire Ebola virus (rVSV-ZEBOV) was created by the Public Health Agency of Canada (PHAC) and is currently licensed in the European Union and United States for the prevention of Ebolavirus Disease (EVD) caused by '' Zaire ebolavirus.''


Serological testing

Pseudotyped viruses, especially pseudotyped viruses carrying a recombinant
luciferase Luciferase is a generic term for the class of oxidative enzymes that produce bioluminescence, and is usually distinguished from a photoprotein. The name was first used by Raphaël Dubois who invented the words ''luciferin'' and ''luciferase'', ...
gene (rLuc), can be used to test whether a treatment can protect host cells infection. For example, blood is drawn from an animal with serological immunity to a virus. A separate pseudovirus is generated with an envelope protein from the virus that the animal has immunity to. The pseudovirus is further engineered to contain a gene for luciferase. When the blood drawn from the animal is mixed with the pseudovirus, the protective antibodies bind and
neutralize Neutralization may refer to: * Neutralization (chemistry), a chemical reaction where a base and an acid react to form a salt * Neutralisation (immunology), pathogen neutralization caused by antibodies * Neutralisation (sociology) * Neutralizati ...
the introduced envelope protein. In
cell culture Cell culture or tissue culture is the process by which cells are grown under controlled conditions, generally outside of their natural environment. The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows. This te ...
, neutralized pseudoviruses will be prevented from infecting cells and producing the luminescent reporter gene product. When analysed, cell culture samples where an effective inhibitor of the virus is present will have reduced luminescence.


References

{{reflist Virology