Influenza (MS 654)☆

R.A. Lamb , K.L. Roberts , in Reference Module in Biomedical Sciences, 2014

Reassortment

Reassortment is the switching of viral RNA (gene) segments in cells infected with two different influenza viruses. The term recombination is often used incorrectly for the process of reassortment. Although reassortment occurs for influenza A, B and C viruses it does not occur among A, B and C virus types. The 1957 and 1968 pandemic viruses have been determined to be reassortments between HA and NA (1957) and HA and PB1 (1967) of avian virus origin into a human virus genetic background and the H5N1 viruses circulating between 1997 and 2007 arose from multiple reassortment events among avian influenza viruses. The H1N1 pd2009 virus is a complex reassortment between human and avian viruses.

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Introduction on Viruses

Sara Momtazmanesh , Nima Rezaei , in Encyclopedia of Infection and Immunity, 2022

Reassortment

Reassortment is exclusively seen in viruses with a segmented genome. It is defined as the exchange of intact genes within the entire segment, which occurs during coinfection. Reassortment has been observed in Bunyaviridae, Reoviruses, arenavirus, and Orthomyxoviruses. Reassortment can result in drastic changes over a short period. For instance, the 2009 novel H1N1 influenza pandemic emerged as a result of a triple reassortment between avian, human, and swine viruses. Antigenic shift, which occurs when a virus has a mixture of surface antigens from two or more viruses, may be a consequence of reassortment (Lowen, 2018; Neumann et al., 2009).

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Arbovirus Evolution

Kathryn A. Hanley , Scott C. Weaver , in Origin and Evolution of Viruses (Second Edition), 2008

Reassortment

Reassortment of gene segments has been shown to occur extensively within the family Bunyaviridae, and occurs efficiently in dually infected mosquitoes when the two different viruses are ingested within 2 days (Borucki et al., 1999). Reassortant bluetongue viruses can be detected in Culicoides variipennis that ingest two different strains within 5 days of each other, while superinfection exclusion prevents reassortment by day 7 (El Hussein et al., 1989). A recombinant Orthobunyavirus (family Bunyaviridae) was recently characterized from hemorrhagic fever cases during an East African epidemic. This virus, Ngari virus, a reassortant with S and L segments derived from bunyamwera virus and an M segment from an unidentified member of the genus, demonstrates the public health importance of arbovirus reassortment (Gerrard et al., 2004). Several examples of reassortment within the group C complex have also been described (Nunes et al., 2005).

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Epidemiology and Control of Viral Diseases

In Fenner's Veterinary Virology (Fifth Edition), 2017

Reassortment

Reassortment is a form of genetic recombination that occurs in RNA viruses with segmented genomes, regardless of whether they are single- or double-stranded and whether these involve few or many segments. Reassortment has been documented in families with 2 (Arenaviridae and Birnaviridae), 3 (Bunyaviridae), 6, 7, or 8 (Orthomyxoviridae), or 10, 11, or 12 (Reoviridae) genome segments. In a cell infected with two related viruses within each of these families, an exchange of segments may occur, with the production of viable and stable reassortants. Such reassortment occurs in nature and is an important source of genetic variability; for example, bluetongue virus strains are often reassortants, sometimes containing genes similar or identical to those of live-attenuated vaccine viruses.

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Viruses as Tools for Vaccine Development

Boriana Marintcheva , in Harnessing the Power of Viruses, 2018

8.4.2.2 Reassortant Vaccines

Reassortant vaccines are manufactured by taking advantage of the natural ability of viruses with segmented genomes to reassort when more than one strain is infecting the host cell. Currently, this approach is applicable to influenza A virus, whose genome is composed of 8 ssRNA segments, and to rotaviruses, harboring a total of 11 dsRNA genomic segments. The goal of reassortment is to "assemble" a virus variant with attenuated pathogenicity that can be used for safe vaccination. Once the desired reassortant is selected, it is propagated in the context of single strain infection, thus preventing the possibility for reversion or drastic changes due to another reassortment event. Two types of reassortant rotavirus vaccines have been developed: one a reassortant of human rotaviruses, and another a reassortant of human and bovine rotaviruses. Efforts are underway to better understand the mechanism of virion packaging in influenza A, B, and C and the relevant packaging signals. It is generally thought that the three types of influenza rarely reassort due to different packing signals. Thus it is possible to utilize influenza C, which causes mild nonseasonal disease and generally does not pose a significant health threat, as a vehicle for influenza A and/or B versions of the flu surface antigens.

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Rotavirus Vaccines

Umesh D. Parashar , ... Paul A. Offit , in Plotkin's Vaccines (Seventh Edition), 2018

Transmission of Vaccine Virus.

Reassortants of G1, G2, G3, and G4 specificity have been administered individually to infants and demonstrated to be as safe as WC3 and, like WC3, to be shed in feces in low incidence (<10%) and at low concentration. 248–251 Therefore, WC3-containing vaccine is much-less-well adapted to growth at the infant intestinal mucosal surface than were RRV-containing vaccines. As a result, horizontal transmission of WC3-based vaccine from immunized infants would seem unlikely. (The initial Phase I study of WC3 rotavirus in infants revealed virus shedding in seven of 22 infants inoculated with 107.5 PFU; no shedding rate of similar magnitude has been noted in any subsequent clinical trial of WC3 or WC3 reassortants.) A report in 2009 described detection of a RotaTeq vaccine-derived strain in a child with gastroenteritis whose sibling had been recently vaccinated with RotaTeq, and further investigation indicated that this strain was generated by further reassortment between two of the reassortant rotavirus strains present in RotaTeq. 303 Additional patients with acute-gastroenteritis and vaccine-derived double-reassortant rotavirus strains have been identified through active surveillance, although it has often been difficult to determine the extent that the rotavirus detected contributed to the patients' symptoms. 304–306

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Rotavirus vaccines

H. Fred Clark , ... Richard L. Ward , in Vaccines (Fifth Edition), 2008

Transmission of vaccine virus

Reassortants of G1, G2, G3, and G4 specificity have been administered individually to infants and demonstrated to be as safe as WC3 and, like WC3, to be shed in feces in low incidence (<10%) and at low concentration. 232–235 Therefore, WC3-containing vaccine is much less well adapted to growth at the infant intestinal mucosal surface than are RRV-containing vaccines. As a result, horizontal transmission of WC3-based vaccine from immunized infants would seem unlikely. (The initial Phase 1 study of WC3 rotavirus in infants revealed virus shedding in 7/22 infants inoculated with 107.5pfu; no shedding rate ofsimilar magnitude has been noted in any subsequent clinical trial of WC3 or WC3 reassortants.)

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Molecular Epidemiology and Evolution of Rotaviruses

K. Bányai , V.E. Pitzer , in Viral Gastroenteritis, 2016

2.2 Reassortment

Reassortment of segmented RNA viruses is a mechanism by which cognate genome segments are exchanged in progeny viruses upon infection of a single cell by two or more closely related virus strains. When these viruses contain different cogent genes, new genotype constellations may emerge. Reassortment of the surface antigens could result in a large number of antigen combinations. However, while over 80 G–P antigen combinations have been identified so far, only six globally common G–P combinations occur in human, globally most common strains, even though many G and P types are expressed by cocirculating strains (Fig. 2.10.1) (Dóró et al., 2014).

Figure 2.10.1. Summary of human G/P genotype combinations found to date.

Color codes: red, globally common; orange, regionally common and unusual; yellow, rare.

The reason behind this phenomenon is unclear. One explanation operates with genetic or phenotypic incompatibility between some variants of the neutralizing antigen specificities (Iturriza-Gómara et al., 2001). An alternative scenario is that there is in vivo selection of combinations that result in masking of VP4 or VP7 neutralization epitopes. Strains hiding their neutralization epitopes after reassortment may evoke a weaker neutralizing antibody response, thus enhancing their fitness over less advantageous antigen combinations (Bányai et al., 2009).

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Reovirus and Rotaviruses

Hoorieh Soleimanjahi , Fatemeh Hosseini Heydarabadi , in Encyclopedia of Infection and Immunity, 2022

Reassortment in segmented dsRNA viruses

Reassortment is a process of genetic recombination that is restricted to segmented RNA viruses and plays a vital role in the evolution of the viruses with pandemic potential in some viruses. Genome segment reassortment occurred during natural infection or trough coculturing of different viruses in the same species, involving the selection and packaging of mRNAs from different parental strains with the same packaging signals (Zafari et al., 2018). The conserved terminal sequences at both ends of RNA segments may be involved as recognition signals for viral transcription, translation, replication, or packaging. The data providing direct evidence of segment reassortment between isolates are only available for viruses in a few genera (Mahy and Regenmortel, 2010; Knipe and Howley, 2013). Closer relations between certain genera have been identified and it has been realized that the nonturreted viruses may represent an ancestral lineage from which the turreted viruses have evolved. For example, comparisons of the polymerase, capping enzyme, and capsid protein sequences, as well as structural analyses of outer capsid proteins, suggest that an evolutionary jump has occurred between the Seadornaviruses and Rotaviruses, within the Sedoreovirinae. This is supposed that gene duplication and rearrangement may occur and cause the changing of the number of genome segments during infection (King et al., 2011).

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A Primer of Molecular Biology

Betsy Foxman , in Molecular Tools and Infectious Disease Epidemiology, 2012

5.5 Recombination

Genetic reassortment, the mixing of genes between two organisms to make a new genetic sequence known as a recombinant, is a powerful mechanism for evolution and adaptation. Sexual reproduction genetically recombines the genes of each parent. Each human is a recombinant of the parents' genes. Fungi reproduce sexually and asexually; when fungi reproduce sexually, the offspring are recombinants. For organisms that do not reproduce sexually, recombination also occurs, but is independent of reproduction.

Sexual reproduction results in large scale rearrangement of DNA during the process of meiosis. Diploid organisms have two copies of each chromosome, with each chromosome carrying a complete set of the same genes. These genes occur in the same order and in the same physical location. Meiosis results in a reassortment of the maternal and paternal chromosomes; the resulting chromosomes have a mix of genes from each parent. Figure 5.4 shows this process for humans; each of the two chromosomes in the daughter cells (meiosis II) are a mix of the original black and white chromosomes, recombinants

Figure 5.4. Meiosis, a type of nuclear division, occurs only in reproductive cells and results in a diploid cell (one having two sets of chromosomes) giving rise to four haploid cells (having a single set of chromosomes). Each haploid cell can subsequently fuse with a gamete of the opposite sex during sexual reproduction. In this illustration, two pairs of homologous chromosomes enter Meiosis I, which results initially in two daughter nuclei, each with two copies of each chromosome. These two cells then enter Meiosis II, producing four daughter nuclei, each with a single copy of each chromosome.

 Source: Reproduced from A Basic Introduction to the Science Underlying NCBI Resources. 9

Viruses do not have a cell and are dependent on the cells they invade to reproduce. However, viruses can create recombinants via a process called genetic reassortment. If two of the same type of virus enter a single cell the genes may genetically reassort, resulting in recombinants. Viruses that infect bacteria, known as bacteriophage or phage, can also pick up bacterial DNA during lysis. Genetic reassortment causes major changes in the influenza A virus, resulting in a genetic shift in the virus and epidemics. Recombination occurs among bacteria by a process known as horizontal gene transfer (described in Section 5.6), which also has been observed among virus and fungi. The creation of bacterial recombinants is an important tool in the molecular biologists toolbox.

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