Chimera (virus)

Virus with genetic material derived from multiple different viruses

This article is about the virus. For other uses, see Chimera.

A chimera or chimeric virus is a virus that contains genetic material derived from two or more distinct viruses. It is defined by the Center for Veterinary Biologics (part of the U.S. Department of Agriculture's Animal and Plant Health Inspection Service) as a "new hybrid microorganism created by joining nucleic acid fragments from two or more different microorganisms in which each of at least two of the fragments contain essential genes necessary for replication."[1] The term genetic chimera had already been defined to mean an individual organism whose body contained cell populations from different zygotes.[2] Chimeric flaviviruses have been created in an attempt to make novel live attenuated vaccines.[3]

## Etymology

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In mythology, a chimera is a creature such as a hippogriff or a gryphon formed from parts of different animals, thus the name for these viruses.

## As a natural phenomenon

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Viruses are categorized in two types: In prokaryotes, the great majority of viruses possess double-stranded (ds) DNA genomes, with a substantial minority of single-stranded (ss) DNA viruses and only limited presence of RNA viruses. In contrast, in eukaryotes, RNA viruses account for the majority of the virome diversity although ssDNA and dsDNA viruses are common as well.[4]

In 2012, the first example of a naturally-occurring RNA-DNA hybrid virus was unexpectedly discovered during a metagenomic study of the acidic extreme environment of Boiling Springs Lake that is in Lassen Volcanic National Park, California.[5][6] The virus was named BSL-RDHV (Boiling Springs Lake RNA DNA Hybrid Virus).[7] Its genome is related to a DNA circovirus, which usually infect birds and pigs, and a RNA tombusvirus, which infect plants. The study surprised scientists, because DNA and RNA viruses vary and the way the chimera came together was not understood.[5][8]

Other viral chimeras have also been found, and the group is known as the CHIV viruses ("chimeric viruses").[4]

## As a bioweapon

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Combining two pathogenic viruses increases the lethality of the new virus[9] which is why there have been cases where chimeric viruses have been considered for use as a bioweapon. For example, the Soviet Union's Chimera Project attempted in the late 1980s and early 1990s to combine DNA from Venezuelan equine encephalitis virus and Smallpox virus at one location, and Ebola virus and Smallpox virus in another location,[10][11] even in the face of Boris Yeltsin's decree of 11 April 1992.

A combination Smallpox virus and Monkeypox virus has also been studied.[9]

## As a medical treatment

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Studies have shown that chimeric viruses can also be developed to have medical benefits. The US Food and Drug Administration (FDA) has recently approved the use of chimeric antigen receptor (CAR) to treat relapsed non-Hodgkin Lymphoma. By introducing a chimeric antigen receptor into T cells, the T cells become more efficient at identifying and attacking the tumor cells.[12] Studies are also in progress to create a chimeric vaccine against four types of Dengue virus, however this has not been successful yet.[13]

## References

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1. ^ Hill, Richard E. Jr (8 December 2005). "Center for Veterinary Biologics Notice No. 05-23" (PDF). United States Department of Agriculture. Animal and Plant Health Inspection Service - Center for Veterinary Biologics. Archived from the original (PDF) on 7 July 2012. Retrieved 5 January 2012.
2. ^ Madan K (September 2020). "Natural human chimeras: A review". Eur J Med Genet. 63 (9): 103971. doi:10.1016/j.ejmg.2020.103971. PMID 32565253.
3. ^ Lai, C. J; Monath, T. P (2003). "Chimeric flaviviruses: novel vaccines against dengue fever, tick-borne encephalitis, and Japanese encephalitis". Adv Virus Res. Advances in Virus Research. 61: 469–509\. doi:10.1016/s0065-3527(03)61013-4. ISBN 9780120398614. PMID 14714441.
4. ^ a b Koonin, Eugene V.; Dolja, Valerian V.; Krupovic, Mart (May 2015). "Origins and evolution of viruses of eukaryotes: The ultimate modularity". Virology. 41 (5): 285–93\. doi:10.2535/ofaj1936.41.5_285. PMID 5898234.
5. ^ a b Diemer, Geoffrey S.; Stedman, Kenneth M. (11 June 2013). "A novel virus genome discovered in an extreme environment suggests recombination between unrelated groups of RNA and DNA viruses". Biology Direct. Retrieved 29 March 2020.
6. ^ Thompson, Helen (20 April 2012). "Hot spring yields hybrid genome: Researchers discover natural chimaeric DNA-RNA virus". Nature. Retrieved 27 March 2020.
7. ^ Devor, Caitlin (12 July 2012)."Scientists discover hybrid virus". Journal of Young Investigators. Retrieved 31 March 2020.
8. ^ BioMed Central Limited (18 April 2012). "Could a newly discovered viral genome change what we thought we knew about virus evolution?". ScienceDaily. Retrieved March 31, 2020.
9. ^ a b Collett, Marc S. (2006). "Impact of Synthetic Genomics on the Threat of Bioterrorism with Viral Agents". Working Papers for Synthetic Genomics: Risks and Benefits for Science and Society: 83–103.
10. ^ Smithson, Amy (1999). "A bio nightmare". Bulletin of the Atomic Scientists. 55 (4): 69–71\. Bibcode:1999BuAtS..55d..69S. doi:10.2968/055004019.
11. ^ Ainscough, Michael J. (2004). "Next Generation Bioweapons: Genetic Engineering and BW" (PDF). Retrieved 9 September 2020.
12. ^ Lulla, Premal D.; Hill, LaQuisa C.; Ramos, Carlos A.; Heslop, Helen E. (2018). "The use of chimeric antigen receptor T cells in patients with non-Hodgkin lymphoma". Clinical Advances in Hematology and Oncology. 16 (5): 375–386\. PMC 6469642. PMID 29851933.
13. ^ US Grant US10053493B2, William Messer; Aravinda De Silva & Boyd Yount, "Methods and compositions for dengue virus vaccines", published 2014, issued 2018, assigned to University of North Carolina at Chapel Hill