Genetic Recombination in Rous Sarcoma Virus: the Genesis of Recombinants and Lack of Evidence for Linkage between pol, env and src Genes in Three Factor Crosses

Wyke, John A.; Beamand, Jennifer A.

doi:10.1099/0022-1317-43-2-349

Cited by 23 publications

(23 citation statements)

References 28 publications

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“…Retroviruses package two complete viral genomic RNAs in each virion, and this specific configuration facilitates recombination by template swapping during reverse transcription. Recombination between retrovirus genomes has been demonstrated during mixed infection with genetically marked avian tumor viruses (4,19,47,53,54), murine leukemia viruses (15,52), and human retroviruses (9). Also, exogenous viruses can recombine with endogenous retrovirus sequences (13,38,49).…”

Section: Discussionmentioning

confidence: 99%

Characterizing and Mapping Porcine Endogenous Retroviruses in Westran Pigs

Lee

Webb

Allen

et al. 2002

J Virol

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Section: Discussionmentioning

confidence: 99%

Characterizing and Mapping Porcine Endogenous Retroviruses in Westran Pigs

Lee

Webb

Allen

et al. 2002

J Virol

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“…In the 1970s, work with animal retroviruses revealed that markers reassorted so readily that they appeared unlinked (334,349). Due to the fact that the retroviral genome is a single RNA and, thus, genes cannot physically reassort, this suggested that retroviruses had evolved to recombine their physically linked genes at an unprecedentedly high rate.…”

Section: Introductionmentioning

confidence: 99%

The Remarkable Frequency of Human Immunodeficiency Virus Type 1 Genetic Recombination

Onafuwa-Nuga

Telesnitsky

2009

Microbiol Mol Biol Rev

147

172

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SUMMARY The genetic diversity of human immunodeficiency virus type 1 (HIV-1) results from a combination of point mutations and genetic recombination, and rates of both processes are unusually high. This review focuses on the mechanisms and outcomes of HIV-1 genetic recombination and on the parameters that make recombination so remarkably frequent. Experimental work has demonstrated that the process that leads to recombination—a copy choice mechanism involving the migration of reverse transcriptase between viral RNA templates—occurs several times on average during every round of HIV-1 DNA synthesis. Key biological factors that lead to high recombination rates for all retroviruses are the recombination-prone nature of their reverse transcription machinery and their pseudodiploid RNA genomes. However, HIV-1 genes recombine even more frequently than do those of many other retroviruses. This reflects the way in which HIV-1 selects genomic RNAs for coencapsidation as well as cell-to-cell transmission properties that lead to unusually frequent associations between distinct viral genotypes. HIV-1 faces strong and changeable selective conditions during replication within patients. The mode of HIV-1 persistence as integrated proviruses and strong selection for defective proviruses in vivo provide conditions for archiving alleles, which can be resuscitated years after initial provirus establishment. Recombination can facilitate drug resistance and may allow superinfecting HIV-1 strains to evade preexisting immune responses, thus adding to challenges in vaccine development. These properties converge to provide HIV-1 with the means, motive, and opportunity to recombine its genetic material at an unprecedented high rate and to allow genetic recombination to serve as one of the highest barriers to HIV-1 eradication.

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“…Others have suggested that more than one copy of the provirus can be formed from one infectious event (10). Retroviruses have also been observed to undergo frequent genetic recombination (11)(12)(13)(14)(15)(16) MATERIALS AND METHODS Definitions. One round of replication is defined as beginning with a provirus in one cell and ending with the formation of a provirus in another cell.…”

mentioning

confidence: 99%

Genetic consequences of packaging two RNA genomes in one retroviral particle: pseudodiploidy and high rate of genetic recombination.

Temin

1990

Proc. Natl. Acad. Sci. U.S.A.

438

353

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Retroviruses contain two complete viral genomic RNAs in each virion. A system to study in a single round ofreplication the products of virions with two different genomic RNAs was established. A spleen necrosis virus-based splicing vector containing both the neomycin-resistance gene (neo) and the hygromycin B phosphotransferase gene (hygro) was used. Two frameshift mutants were derived from this vector such that the neo and the hygro genes were inactivated in separate vectors. Thus, each vector confers resistance to only one selection. The vectors with frameshift mutations were separately propagated and were pooled to infect DSDh helper cells. Doubly resistant cell clones were isolated, and viruses produced from these clones were used to infect D17 cells. This protocol allowed virions containing two different genomic RNAs (heterozygotes) to complete one round ofretroviral replication. The molecular nature of progeny that conferred resistance to single or double selection and their ratio were determined. Our data demonstrate that each infectious heterozygous virion produces only one provirus. The rate of retroviral recombination is =2% per kilobase per replication cycle. Recombinant proviruses are progeny of heterozygous virions.The retroviral life cycle requires DNA molecules to be copied from viral RNA and to integrate into the host genome to form the provirus (1). However, a unique feature of retroviruses is that two RNA genomes are packaged in one virion (2-7). It has been suggested that one provirus is formed from the two copies ofgenomic RNA in one virion; that is, retroviruses are pseudodiploids (8,9). Others have suggested that more than one copy of the provirus can be formed from one infectious event (10). Retroviruses have also been observed to undergo frequent genetic recombination (11)(12)(13)(14)(15)(16) MATERIALS AND METHODS Definitions. One round of replication is defined as beginning with a provirus in one cell and ending with the formation of a provirus in another cell. Thus, the events in one round of replication include RNA transcription of the proviral DNA, assembly of the virus, entry of virus into a host cell, reverse transcription of the genome, and integration. Rate refers to the frequency of events -occurring in one round of replication. Rate ofrecombination is calculated by comparing the titer of doubly resistant colonies (recombinant phenotype) with the lower titer of the two types of singly resistant colonies (parental phenotypes). The titers of the doubly resistant colonies were determined from the linear range of a series of 10-fold dilutions.Plasmid Construction. pWH12, pWH13, and pWH14 were derived from pJD216NeoHy (17). pJD216NeoHy was partially digested with Nco I, and the resulting recessed 3' ends were filled in by the Klenow fragment of Escherichia coli DNA polymerase I. These products were ligated and were used to transform competent E. coli cells. This approach resulted in two plasmids, pWH13 and pWH14. Each contained a 4-base pair (bp) insertion in either the neo (pW...

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Genetic Recombination in Rous Sarcoma Virus: the Genesis of Recombinants and Lack of Evidence for Linkage between pol, env and src Genes in Three Factor Crosses

Cited by 23 publications

References 28 publications

Characterizing and Mapping Porcine Endogenous Retroviruses in Westran Pigs

Characterizing and Mapping Porcine Endogenous Retroviruses in Westran Pigs

The Remarkable Frequency of Human Immunodeficiency Virus Type 1 Genetic Recombination

Genetic consequences of packaging two RNA genomes in one retroviral particle: pseudodiploidy and high rate of genetic recombination.

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