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'''Pseudotyping''' is the process of producing [[viruses]] or [[viral vector]]s in combination with foreign [[viral envelope|viral envelope proteins]]. The result is a pseudotyped virus particle.<ref>[http://www99.mh-hannover.de/institute/virologie/section/retro/retro_en.html Example for the development of pseudotype retroviral vectors in a work group of MHH] {{webarchive|url=https://web.archive.org/web/20091108024125/http://www99.mh-hannover.de/institute/virologie/section/retro/retro_en.html |date=2009-11-08 }}</ref> With this method, the foreign viral envelope proteins can be used to alter [[host tropism]] or |
'''Pseudotyping''' is the process of producing [[viruses]] or [[viral vector]]s in combination with foreign [[viral envelope|viral envelope proteins]]. The result is a pseudotyped virus particle, also called a pseudovirus.<ref>[http://www99.mh-hannover.de/institute/virologie/section/retro/retro_en.html Example for the development of pseudotype retroviral vectors in a work group of MHH] {{webarchive|url=https://web.archive.org/web/20091108024125/http://www99.mh-hannover.de/institute/virologie/section/retro/retro_en.html |date=2009-11-08 }}</ref> 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 [[Phenotype|phenotypic]] changes cannot be passed on to progeny viral particles. In some cases, the inability to produce viral envelope proteins renders the pseudovirus [[Viral replication|replication incompetent]]. In this way, the properties of [[BSL 4|dangerous viruses]] can be studied in a lower risk setting<ref name=":0">{{Cite journal|last=Nie|first=Jianhui|last2=Liu|first2=Lin|last3=Wang|first3=Qing|last4=Chen|first4=Ruifeng|last5=Ning|first5=Tingting|last6=Liu|first6=Qiang|last7=Huang|first7=Weijin|last8=Wang|first8=Youchun|date=2019-02-19|title=Nipah pseudovirus system enables evaluation of vaccines in vitro and in vivo using non-BSL-4 facilities|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6455126/|journal=Emerging Microbes & Infections|volume=8|issue=1|pages=272–281|doi=10.1080/22221751.2019.1571871|issn=2222-1751|pmc=6455126|pmid=30866781}}</ref>. |
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Pseudotyping allows one to control the expression of envelope proteins. A frequently used protein is the [[Glycoprotein|glycoprotein G]] (VSV-G) from the [[Vesicular stomatitis virus]] (VSV) which mediates entry via the [[LDL receptor]]. Envelope proteins incorporated into the pseudovirus allow the virus to [[Viral entry|readily enter]] different [[cell type]]s with the corresponding host [[Receptor (biochemistry)|receptor]]. |
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== Vaccine Development == |
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Pseudotyped virus can be used to vaccinate animals against proteins expressed the envelope of the virion.<ref name=":1">{{Cite journal|last=Racine|first=Trina|last2=Kobinger|first2=Gary P.|last3=Arts|first3=Eric J.|date=2017-09-12|title=Development of an HIV vaccine using a vesicular stomatitis virus vector expressing designer HIV-1 envelope glycoproteins to enhance humoral responses|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5594459/|journal=AIDS Research and Therapy|volume=14|doi=10.1186/s12981-017-0179-2|issn=1742-6405|pmc=5594459|pmid=28893277}}</ref> This approach has been used to produce vaccine candidates against [[HIV]]<ref name=":1" />, [[Nipah virus (virus)|Nipah virus]]<ref name=":0" />, [[Rabies lyssavirus]]<ref name=":2">{{Cite journal|last=Moeschler|first=Sarah|last2=Locher|first2=Samira|last3=Conzelmann|first3=Karl-Klaus|last4=Krämer|first4=Beate|last5=Zimmer|first5=Gert|date=2016-09-16|title=Quantification of Lyssavirus-Neutralizing Antibodies Using Vesicular Stomatitis Virus Pseudotype Particles|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5035968/|journal=Viruses|volume=8|issue=9|doi=10.3390/v8090254|issn=1999-4915|pmc=5035968|pmid=27649230}}</ref>, [[SARS-CoV|SARS-CoV,]]<ref>{{Cite journal|last=Kapadia|first=Sagar U.|last2=Simon|first2=Ian D.|last3=Rose|first3=John K.|date=2008-06-20|title=SARS vaccine based on a replication-defective recombinant vesicular stomatitis virus is more potent than one based on a replication-competent vector|url=http://www.sciencedirect.com/science/article/pii/S0042682208001736|journal=Virology|language=en|volume=376|issue=1|pages=165–172|doi=10.1016/j.virol.2008.03.002|issn=0042-6822}}</ref> and ''[[Zaire ebolavirus|Zaire Ebolavirus]]''<ref>{{Cite journal|last=Salata|first=Cristiano|last2=Calistri|first2=Arianna|last3=Alvisi|first3=Gualtiero|last4=Celestino|first4=Michele|last5=Parolin|first5=Cristina|last6=Palù|first6=Giorgio|date=2019-03-19|title=Ebola Virus Entry: From Molecular Characterization to Drug Discovery|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466262/|journal=Viruses|volume=11|issue=3|doi=10.3390/v11030274|issn=1999-4915|pmc=6466262|pmid=30893774}}</ref>. [[RVSV-ZEBOV vaccine|Recombinant vesicular stomatitis virus–Zaire Ebola virus (rVSV-ZEBOV)]] was created by the [[Public Health Agency of Canada|Public Health Agency Canada (PHAC)]] and is currently licensed in the European Union and United States for the prevention of [[Ebola virus disease|Ebolavirus Disease]] (EVD) caused by ''[[Zaire ebolavirus|Zaire Ebolavirus]].'' |
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== Serological Testing == |
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Pseudotyped viruses, especially pseudotyped viruses carrying a [[Recombinant virus|recombinant]] [[luciferase]] gene (rLuc), can be used to test whether a treatment can protect host cells infection<ref>{{Cite journal|last=Carnell|first=George William|last2=Ferrara|first2=Francesca|last3=Grehan|first3=Keith|last4=Thompson|first4=Craig Peter|last5=Temperton|first5=Nigel James|date=2015-04-29|title=Pseudotype-Based Neutralization Assays for Influenza: A Systematic Analysis|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413832/|journal=Frontiers in Immunology|volume=6|doi=10.3389/fimmu.2015.00161|issn=1664-3224|pmc=4413832|pmid=25972865}}</ref>. For example, blood drawn from an animal with [[serological]] immunity to a virus. A separate pseudotype particle is generated with an envelope protein that the animal has immunity to. When the blood drawn from the animal is mixed with the pseudotype particle, the [[Antibody|protective antibodies]] bind and [[Neutralizing antibody|neutralize]] the introduced envelope protein. In [[cell culture]], neutralized pseudotyped viruses will be [[Viral entry|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<ref name=":2" />. |
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== References == |
== References == |
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Revision as of 20:24, 7 May 2020
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Pseudotyping is the process of producing viruses or viral vectors in combination with foreign viral envelope proteins. The result is a pseudotyped virus particle, also called a pseudovirus.[1] 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[2].
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. Envelope proteins incorporated into the pseudovirus allow the virus to readily enter different cell types with the corresponding host receptor.
Vaccine Development
Pseudotyped virus can be used to vaccinate animals against proteins expressed the envelope of the virion.[3] This approach has been used to produce vaccine candidates against HIV[3], Nipah virus[2], Rabies lyssavirus[4], SARS-CoV,[5] and Zaire Ebolavirus[6]. Recombinant vesicular stomatitis virus–Zaire Ebola virus (rVSV-ZEBOV) was created by the Public Health Agency 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 gene (rLuc), can be used to test whether a treatment can protect host cells infection[7]. For example, blood drawn from an animal with serological immunity to a virus. A separate pseudotype particle is generated with an envelope protein that the animal has immunity to. When the blood drawn from the animal is mixed with the pseudotype particle, the protective antibodies bind and neutralize the introduced envelope protein. In cell culture, neutralized pseudotyped viruses 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[4].
References
- ^ Example for the development of pseudotype retroviral vectors in a work group of MHH Archived 2009-11-08 at the Wayback Machine
- ^ a b Nie, Jianhui; Liu, Lin; Wang, Qing; Chen, Ruifeng; Ning, Tingting; Liu, Qiang; Huang, Weijin; Wang, Youchun (2019-02-19). "Nipah pseudovirus system enables evaluation of vaccines in vitro and in vivo using non-BSL-4 facilities". Emerging Microbes & Infections. 8 (1): 272–281. doi:10.1080/22221751.2019.1571871. ISSN 2222-1751. PMC 6455126. PMID 30866781.
- ^ a b Racine, Trina; Kobinger, Gary P.; Arts, Eric J. (2017-09-12). "Development of an HIV vaccine using a vesicular stomatitis virus vector expressing designer HIV-1 envelope glycoproteins to enhance humoral responses". AIDS Research and Therapy. 14. doi:10.1186/s12981-017-0179-2. ISSN 1742-6405. PMC 5594459. PMID 28893277.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ a b Moeschler, Sarah; Locher, Samira; Conzelmann, Karl-Klaus; Krämer, Beate; Zimmer, Gert (2016-09-16). "Quantification of Lyssavirus-Neutralizing Antibodies Using Vesicular Stomatitis Virus Pseudotype Particles". Viruses. 8 (9). doi:10.3390/v8090254. ISSN 1999-4915. PMC 5035968. PMID 27649230.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Kapadia, Sagar U.; Simon, Ian D.; Rose, John K. (2008-06-20). "SARS vaccine based on a replication-defective recombinant vesicular stomatitis virus is more potent than one based on a replication-competent vector". Virology. 376 (1): 165–172. doi:10.1016/j.virol.2008.03.002. ISSN 0042-6822.
- ^ Salata, Cristiano; Calistri, Arianna; Alvisi, Gualtiero; Celestino, Michele; Parolin, Cristina; Palù, Giorgio (2019-03-19). "Ebola Virus Entry: From Molecular Characterization to Drug Discovery". Viruses. 11 (3). doi:10.3390/v11030274. ISSN 1999-4915. PMC 6466262. PMID 30893774.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Carnell, George William; Ferrara, Francesca; Grehan, Keith; Thompson, Craig Peter; Temperton, Nigel James (2015-04-29). "Pseudotype-Based Neutralization Assays for Influenza: A Systematic Analysis". Frontiers in Immunology. 6. doi:10.3389/fimmu.2015.00161. ISSN 1664-3224. PMC 4413832. PMID 25972865.
{{cite journal}}: CS1 maint: unflagged free DOI (link)
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