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Genome sequence of SG33 strain and recombination between wild-type and vaccine myxoma viruses.

ABSTRACT: Myxomatosis in Europe is the result of the release of a South America strain of myxoma virus in 1952. Several attenuated strains with origins in South America or California have since been used as vaccines in the rabbit industry. We sequenced the genome of the SG33 myxoma virus vaccine strain and compared it with those of other myxoma virus strains. We show that SG33 genome carries a large deletion in its right end. Furthermore, our data strongly suggest that the virus isolate from which SG33 is derived results from an in vivo recombination between a wild-type South America (Lausanne) strain and a California MSD-derived strain. These findings raise questions about the use of insufficiently attenuated virus in vaccination.

SUBMITTER: Camus-Bouclainville C

PROVIDER: S-EPMC3377406 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Genome sequence of SG33 strain and recombination between wild-type and vaccine myxoma viruses.

Camus-Bouclainville Christelle C Gretillat Magalie M Py Robert R Gelfi Jacqueline J Guérin Jean Luc JL Bertagnoli Stéphane S

Emerging infectious diseases 20110401 4

Myxomatosis in Europe is the result of the release of a South America strain of myxoma virus in 1952. Several attenuated strains with origins in South America or California have since been used as vaccines in the rabbit industry. We sequenced the genome of the SG33 myxoma virus vaccine strain and compared it with those of other myxoma virus strains. We show that SG33 genome carries a large deletion in its right end. Furthermore, our data strongly suggest that the virus isolate from which SG33 is ...[more]

PMID: 21470452

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Project description:UnlabelledRecombination plays a critical role in virus evolution. It helps avoid genetic decline and creates novel phenotypes. This promotes survival, and genome sequencing suggests that recombination has facilitated the evolution of human pathogens, including orthopoxviruses such as variola virus. Recombination can also be used to map genes, but although recombinant poxviruses are easily produced in culture, classical attempts to map the vaccinia virus (VACV) genome this way met with little success. We have sequenced recombinants formed when VACV strains TianTan and Dryvax are crossed under different conditions. These were a single round of growth in coinfected cells, five rounds of sequential passage, or recombinants obtained using leporipoxvirus-mediated DNA reactivation. Our studies showed that recombinants contain a patchwork of DNA, with the number of exchanges increasing with passage. Further passage also selected for TianTan DNA and correlated with increased plaque size. The recombinants produced through a single round of coinfection contain a disproportionate number of short conversion tracks (<1 kbp) and exhibited 1 exchange per 12 kbp, close to the ∼1 per 8 kbp in the literature. One by-product of this study was that rare mutations were also detected; VACV replication produces ∼1×10(-8) mutation per nucleotide copied per cycle of replication and ∼1 large (21 kbp) deletion per 70 rounds of passage. Viruses produced using DNA reactivation appeared no different from recombinants produced using ordinary methods. An attractive feature of this approach is that when it is combined with selection for a particular phenotype, it provides a way of mapping and dissecting more complex virus traits.ImportanceWhen two closely related viruses coinfect the same cell, they can swap genetic information through a process called recombination. Recombination produces new viruses bearing different combinations of genes, and it plays an important role in virus evolution. Poxviruses are a family of viruses that includes variola (or smallpox) virus, and although poxviruses are known to recombine, no one has previously mapped the patterns of DNAs exchanged between viruses. We coinfected cells with two different vaccinia poxviruses, isolated the progeny, and sequenced them. We show that poxvirus recombination is a very accurate process that assembles viruses containing DNA copied from both parents. In a single round of infection, DNA is swapped back and forth ∼18 times per genome to make recombinant viruses that are a mosaic of the two parental DNAs. This mixes many different genes in complex combinations and illustrates how recombination can produce viruses with greatly altered disease potential.

Dataset Information

Genome sequence of SG33 strain and recombination between wild-type and vaccine myxoma viruses.

Publications

Genome sequence of SG33 strain and recombination between wild-type and vaccine myxoma viruses.

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