Chimera (virus)

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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 or an organism that developed from portions of different embryos.[ citation needed ] Chimeric flaviviruses have been created in an attempt to make novel live attenuated vaccines. [2]

Contents

Etymology

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

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. [3]

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. [4] [5] The virus was named BSL-RDHV (Boiling Springs Lake RNA DNA Hybrid Virus). [6] 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. [4] [7]

Other viral chimeras have also been found, and the group is known as the CHIV viruses ("chimeric viruses"). [3]

As a bioweapon

Combining two pathogenic viruses increases the lethality of the new virus [8] 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, [9] [10] even in the face of Boris Yeltsin's decree of 11 April 1992.

A combination Smallpox virus and Monkeypox virus has also been studied. [8]

As a medical treatment

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. [11] Studies are also in progress to create a chimeric vaccine against four types of Dengue virus, however this has not been successful yet. [12]

Related Research Articles

<span class="mw-page-title-main">DNA vaccine</span> Vaccine containing DNA

A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.

<i>Flaviviridae</i> Family of viruses

Flaviviridae is a family of enveloped positive-strand RNA viruses which mainly infect mammals and birds. They are primarily spread through arthropod vectors. The family gets its name from the yellow fever virus; flavus is Latin for "yellow", and yellow fever in turn was named because of its propensity to cause jaundice in victims. There are 89 species in the family divided among four genera. Diseases associated with the group include: hepatitis (hepaciviruses), hemorrhagic syndromes, fatal mucosal disease (pestiviruses), hemorrhagic fever, encephalitis, and the birth defect microcephaly (flaviviruses).

<span class="mw-page-title-main">Chimera (genetics)</span> Single organism composed of two or more different populations of genetically distinct cells

A genetic chimerism or chimera is a single organism composed of cells with more than one distinct genotype. Animal chimeras can be produced by the fusion of two embryos. In plants and some animal chimeras, mosaicism involves distinct types of tissue that originated from the same zygote but differ due to mutation during ordinary cell division.

Viral evolution is a subfield of evolutionary biology and virology that is specifically concerned with the evolution of viruses. Viruses have short generation times, and many—in particular RNA viruses—have relatively high mutation rates. Although most viral mutations confer no benefit and often even prove deleterious to viruses, the rapid rate of viral mutation combined with natural selection allows viruses to quickly adapt to changes in their host environment. In addition, because viruses typically produce many copies in an infected host, mutated genes can be passed on to many offspring quickly. Although the chance of mutations and evolution can change depending on the type of virus, viruses overall have high chances for mutations.

<i>Flavivirus</i> Genus of viruses

Flavivirus, renamed Orthoflavivirus in 2023, is a genus of positive-strand RNA viruses in the family Flaviviridae. The genus includes the West Nile virus, dengue virus, tick-borne encephalitis virus, yellow fever virus, Zika virus and several other viruses which may cause encephalitis, as well as insect-specific flaviviruses (ISFs) such as cell fusing agent virus (CFAV), Palm Creek virus (PCV), and Parramatta River virus (PaRV). While dual-host flaviviruses can infect vertebrates as well as arthropods, insect-specific flaviviruses are restricted to their competent arthropods. The means by which flaviviruses establish persistent infection in their competent vectors and cause disease in humans depends upon several virus-host interactions, including the intricate interplay between flavivirus-encoded immune antagonists and the host antiviral innate immune effector molecules.

Antigenic drift is a kind of genetic variation in viruses, arising from the accumulation of mutations in the virus genes that code for virus-surface proteins that host antibodies recognize. This results in a new strain of virus particles that is not effectively inhibited by the antibodies that prevented infection by previous strains. This makes it easier for the changed virus to spread throughout a partially immune population. Antigenic drift occurs in both influenza A and influenza B viruses.

ATC code J07Vaccines is a therapeutic subgroup of the Anatomical Therapeutic Chemical Classification System, a system of alphanumeric codes developed by the World Health Organization (WHO) for the classification of drugs and other medical products. Subgroup J07 is part of the anatomical group J Antiinfectives for systemic use.

<i>Dengue virus</i> Species of virus

Dengue virus (DENV) is the cause of dengue fever. It is a mosquito-borne, single positive-stranded RNA virus of the family Flaviviridae; genus Flavivirus. Four serotypes of the virus have been found, and a reported fifth has yet to be confirmed, all of which can cause the full spectrum of disease. Nevertheless, the mainstream scientific community's understanding of dengue virus may be simplistic as, rather than distinct antigenic groups, a continuum appears to exist. This same study identified 47 strains of dengue virus. Additionally, coinfection with and lack of rapid tests for Zika virus and chikungunya complicate matters in real-world infections.

Virotherapy is a treatment using biotechnology to convert viruses into therapeutic agents by reprogramming viruses to treat diseases. There are three main branches of virotherapy: anti-cancer oncolytic viruses, viral vectors for gene therapy and viral immunotherapy. These branches use three different types of treatment methods: gene overexpression, gene knockout, and suicide gene delivery. Gene overexpression adds genetic sequences that compensate for low to zero levels of needed gene expression. Gene knockout uses RNA methods to silence or reduce expression of disease-causing genes. Suicide gene delivery introduces genetic sequences that induce an apoptotic response in cells, usually to kill cancerous growths. In a slightly different context, virotherapy can also refer more broadly to the use of viruses to treat certain medical conditions by killing pathogens.

<i>Tick-borne encephalitis virus</i> Species of virus

Tick-borne encephalitis virus (TBEV) is a positive-strand RNA virus associated with tick-borne encephalitis in the genus Flavivirus.

<i>Alphavirus</i> Genus of viruses

Alphavirus is a genus of RNA viruses, the sole genus in the Togaviridae family. Alphaviruses belong to group IV of the Baltimore classification of viruses, with a positive-sense, single-stranded RNA genome. There are 32 alphavirus species, which infect various vertebrates such as humans, rodents, fish, birds, and larger mammals such as horses, as well as invertebrates. Alphaviruses that can infect both vertebrates and arthropods are referred dual-host alphaviruses, while insect-specific alphaviruses such as Eilat virus and Yada yada virus are restricted to their competent arthropod vector. Transmission between species and their vertebrate hosts occurs mainly via mosquitoes, making the alphaviruses a member of the collection of arboviruses – or arthropod-borne viruses. Alphavirus particles are enveloped, have a 70 nm diameter, tend to be spherical, and have a 40 nm isometric nucleocapsid.

<span class="mw-page-title-main">Viral vector</span> Biotechnology to deliver genetic material into a cell

Viral vectors are modified viruses designed to deliver genetic material into cells. This process can be performed inside an organism or in cell culture. Viral vectors have widespread applications in basic research, agriculture, and medicine.

Antigenic variation or antigenic alteration refers to the mechanism by which an infectious agent such as a protozoan, bacterium or virus alters the proteins or carbohydrates on its surface and thus avoids a host immune response, making it one of the mechanisms of antigenic escape. It is related to phase variation. Antigenic variation not only enables the pathogen to avoid the immune response in its current host, but also allows re-infection of previously infected hosts. Immunity to re-infection is based on recognition of the antigens carried by the pathogen, which are "remembered" by the acquired immune response. If the pathogen's dominant antigen can be altered, the pathogen can then evade the host's acquired immune system. Antigenic variation can occur by altering a variety of surface molecules including proteins and carbohydrates. Antigenic variation can result from gene conversion, site-specific DNA inversions, hypermutation, or recombination of sequence cassettes. The result is that even a clonal population of pathogens expresses a heterogeneous phenotype. Many of the proteins known to show antigenic or phase variation are related to virulence.

<span class="mw-page-title-main">Veterinary virology</span> Study of viruses affecting animals

Veterinary virology is the study of viruses in non-human animals. It is an important branch of veterinary medicine.

<span class="mw-page-title-main">Virus</span> Infectious agent that replicates in cells

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 almost every ecosystem on Earth and are the most numerous type of biological entity. Since Dmitri Ivanovsky's 1892 article describing a non-bacterial pathogen infecting tobacco plants and the discovery of the tobacco mosaic virus by Martinus Beijerinck in 1898, more than 11,000 of the millions of virus species have been described in detail. The study of viruses is known as virology, a subspeciality of microbiology.

<span class="mw-page-title-main">Genetically modified virus</span> Species of virus

A genetically modified virus is a virus that has been altered or generated using biotechnology methods, and remains capable of infection. Genetic modification involves the directed insertion, deletion, artificial synthesis or change of nucleotide bases in viral genomes. Genetically modified viruses are mostly generated by the insertion of foreign genes intro viral genomes for the purposes of biomedical, agricultural, bio-control, or technological objectives. The terms genetically modified virus and genetically engineered virus are used synonymously.

In biology, a pathogen, in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ.

This glossary of virology is a list of definitions of terms and concepts used in virology, the study of viruses, particularly in the description of viruses and their actions. Related fields include microbiology, molecular biology, and genetics.

<i>West Nile virus</i> Species of flavivirus causing West Nile fever

West Nile virus (WNV) is a single-stranded RNA virus that causes West Nile fever. It is a member of the family Flaviviridae, from the genus Flavivirus, which also contains the Zika virus, dengue virus, and yellow fever virus. The virus is primarily transmitted by mosquitoes, mostly species of Culex. The primary hosts of WNV are birds, so that the virus remains within a "bird–mosquito–bird" transmission cycle. The virus is genetically related to the Japanese encephalitis family of viruses. Humans and horses both exhibit disease symptoms from the virus, and symptoms rarely occur in other animals.

<i>Modoc virus</i> Species of virus

Modoc virus (MODV) is a rodent-associated flavivirus. Small and enveloped, MODV contains positive single-stranded RNA. Taxonomically, MODV is part of the Flavivirus genus and Flaviviridae family. The Flavivirus genus includes nearly 80 viruses, both vector-borne and no known vector (NKV) species. Known flavivirus vector-borne viruses include Dengue virus, Yellow Fever virus, tick-borne encephalitis virus, and West Nile virus.

References

  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. ↑ 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.
  3. 1 2 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.
  4. 1 2 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.
  5. ↑ Thompson, Helen (20 April 2012). "Hot spring yields hybrid genome: Researchers discover natural chimaeric DNA-RNA virus". Nature. Retrieved 27 March 2020.
  6. ↑ Devor, Caitlin (12 July 2012)."Scientists discover hybrid virus". Journal of Young Investigators. Retrieved 31 March 2020.
  7. ↑ 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.
  8. 1 2 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.
  9. ↑ Smithson, Amy (1999). "A bio nightmare". Bulletin of the Atomic Scientists. 55 (4): 69–71. Bibcode:1999BuAtS..55d..69S. doi:10.2968/055004019.
  10. ↑ Ainscough, Michael J. (2004). "Next Generation Bioweapons: Genetic Engineering and BW" (PDF). Retrieved 9 September 2020.
  11. ↑ 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.
  12. ↑ USGrant 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
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