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Pseudotyping is the process of producing
viruses A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are found in almo ...
or
viral vector A viral vector is a modified virus designed to gene delivery, deliver genetic material into cell (biology), cells. This process can be performed inside an organism or in cell culture. Viral vectors have widespread applications in basic research, ...
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 In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological propert ...
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 (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 type A cell type is a classification used to identify cells that share morphological or phenotypical features. A multicellular organism may contain cells of a number of widely differing and specialized cell types, such as muscle cells and skin cell ...
s with the corresponding host
receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...
.


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, ''
Zaire ebolavirus ''Orthoebolavirus zairense'' or Zaire ebolavirus, more commonly known as Ebola virus (; EBOV), is one of six known species within the genus ''Ebolavirus''. Four of the six known ebolaviruses, including EBOV, cause a severe and often fatal hem ...
,'' and
SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19, the respiratory illness responsible for the COVID-19 pandemic. The virus previously had the Novel coronavirus, provisional nam ...
. 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 ''Orthoebolavirus zairense'' or Zaire ebolavirus, more commonly known as Ebola virus (; EBOV), is one of six known species within the genus ''Ebolavirus''. Four of the six known ebolaviruses, including EBOV, cause a severe and often fatal hem ...
.''


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 Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mi ...
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 the introduced envelope protein. In
cell culture Cell culture or tissue culture is the process by which cell (biology), cells are grown under controlled conditions, generally outside of their natural environment. After cells of interest have been Cell isolation, isolated from living tissue, ...
, 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