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. Since Dmitri Ivanovsky's ...

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 molecu ...

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 Host tropism is the infection specificity of certain pathogens to particular hosts and host tissues. This explains why most pathogens are only capable of infecting a limited range of host organisms. Researchers can classify pathogenic organisms ...

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 pi ...

(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 t ...

. 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 cells, ...

s with the corresponding host receptor.

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 The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...

, ''Nipah henipavirus'', ''

Rabies lyssavirus Rabies virus, scientific name ''Rabies lyssavirus'', is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. ''Rabies lyss ...

'', SARS-CoV, ''

Zaire ebolavirus ''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 hemorrhagic fever in humans and ot ...

,'' and

SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a ...

. 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 ''

.''

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 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 t ...

, 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