Phylogenetic analysis reveals a low rate of homologous recombination in negative-sense RNA viruses

Chare, Elizabeth R.; Gould, Ernest A.; Holmes, Edward C.

doi:10.1099/vir.0.19277-0

Cited by 253 publications

(213 citation statements)

References 61 publications

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“…In future research, we hope to address the potential fitness benefits (or costs) of recombination in ZEBOV, as well as to describe the molecular mechanisms underlying it. Our finding represents the first evidence of a recombination event within the Filoviridae family (Ebola and Marburg viruses) and one of only a few examples of such an event in negative-strand RNA viruses (17). This result has important implications for vaccine development (18,19) because it raises the possibility of recombination between a live attenuated vaccine strain and wild-type strains, a scenario that could have grave public health repercussions.…”

Section: Discussionmentioning

confidence: 93%

Isolates of Zaire ebolavirus from wild apes reveal genetic lineage and recombinants

Wittmann

Biek

Hassanin

et al. 2007

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

107

114

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Over the last 30 years, Zaire ebolavirus (ZEBOV), a virus highly pathogenic for humans and wild apes, has emerged repeatedly in Central Africa. Thus far, only a few virus isolates have been characterized genetically, all belonging to a single genetic lineage and originating exclusively from infected human patients. Here, we describe the first ZEBOV sequences isolated from great ape carcasses in the Gabon/Congo region that belong to a previously unrecognized genetic lineage. According to our estimates, this lineage, which we also encountered in the two most recent human outbreaks in the Republic of the Congo in 2003 and 2005, diverged from the previously known viruses around the time of the first documented human outbreak in 1976. These results suggest that virus spillover from the reservoir has occurred more than once, as predicted by the multiple emergence hypothesis. However, the young age of both ZEBOV lineages and the spatial and temporal sequence of outbreaks remain at odds with the idea that the virus simply emerged from a long-established and widespread reservoir population. Based on data from two ZEBOV genes, we also demonstrate, within the family Filoviridae , recombination between the two lineages. According to our estimates, this event took place between 1996 and 2001 and gave rise to a group of recombinant viruses that were responsible for a series of outbreaks in 2001–2003. The potential for recombination adds an additional level of complexity to unraveling and potentially controlling the emergence of ZEBOV in humans and wildlife species.

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Section: Discussionmentioning

confidence: 93%

Isolates of Zaire ebolavirus from wild apes reveal genetic lineage and recombinants

Wittmann

Biek

Hassanin

et al. 2007

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

107

114

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“…Mutation rates in VSV are comparable to those in other RNA viruses (11). The virus is effectively asexual, as there is no significant amount of recombination (3,28,29). VSV has been used as a model to study general principles of evolutionary genetics and the particular rules governing the evolution of RNA viruses (reviewed in reference 8).…”

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confidence: 99%

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confidence: 99%

Density-Dependent Selection in Vesicular Stomatitis Virus

Novella

Reissig

Wilke

2004

J Virol

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We used vesicular stomatitis virus to test the effect of complementation on the relative fitness of a deleterious mutant, monoclonal antibody-resistant mutant (MARM) N, in competition with its wild-type ancestor. We carried out competitions of MARM N and wild-type populations at different multiplicities of infection (MOIs) and initial ratios of the wild type to the mutant and found that the fitness of MARM N relative to that of the wild type is very sensitive to changes in the MOI (i.e., the degree of complementation) but depends little, if at all, on the initial frequencies of MARM N and the wild type. Further, we developed a mathematical model under the assumption that during coinfection both viruses contribute to a common pool of protein products in the infected cell and that they both exploit this common pool equally. Under such conditions, the fitness of all virions that coinfect a cell is the average fitness in the absence of coinfection of that group of virions. In the absence of coinfection, complementation cannot take place and the relative fitness of each competitor is only determined by the selective value of its own products. We found good agreement between our experimental results and the model predictions, which suggests that the wild type and MARM N freely share all of their gene products under coinfection.RNA viruses form highly polymorphic populations called quasispecies (8,9,13). The origin of much of their genetic diversity is high mutational pressure. Most RNA viruses have mutation rates on the order of one miscopied base per genome and generation (10, 11). However, high mutational pressure is not necessarily the only factor promoting genetic diversity. Niche differentiation can allow stable polymorphisms in an infected host. For instance, during a polyclonal immune response, different subpopulations may have different sensitivities to individual antibodies; variation within a host can also be related to differences in the tropism of different viral subpopulations. Virus-virus interactions may also promote stable polymorphisms in an infected host. In cell culture, such interactions readily occur during replication inside a cell and are likely to be an important contributor to the maintenance of variation. When two or more virions coinfect the same cell, complementation can take place. Not every function can be complemented in trans. In positive-stranded viruses, translation and replication are coupled (25); therefore, many functions need to be provided in cis and cannot be rescued by complementation (33, 37). Other proteins can freely interact with heterologous genomes or replicons, even from different viral species (18,21). In the absence of compartmentalization or other limitations to the diffusion of viral products, soluble proteins can interact with any genome inside the cell, potentially changing the phenotype of the virions and masking targets for natural selection to operate. A remarkable example of this phenomenon is phenotypic mixing and hiding, particularly for monoclonal antibody (...

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“…Proportionally, the amount of genetic variability produced after a single recombination event is larger than that produced by single point mutations. Although the importance of recombination was underappreciated in early studies of virus genome evolution, it is now recognized as a widespread phenomenon among positive-strand RNA viruses in animals (Grassly & Holmes, 1997;Holmes et al, 1999;Wilson et al, 1988) and plants (Nagy & Bujarski, 1993;Revers et al, 1996;Aranda et al, 1997;Olsthoorn et al, 2002;Bousalem et al, 2003;Cheng & Nagy, 2003;Moreno et al, 2004;Tan et al, 2004;Bonnet et al, 2005;Urbanowicz et al, 2005;Chare & Holmes, 2006;Weng et al, 2007), as well as in retroviruses such as human immunodeficiency virus type 1 Prljic et al, 2004;Althaus & Bonhoeffer, 2005;Galetto & Negroni, 2005), although it is a rare or even non-existent phenomenon among negativestrand viruses (Chare et al, 2003). There are several mechanisms by which RNA recombination may take place, the most common of which is homologous recombination (Lai, 1992).…”

Section: Introductionmentioning

confidence: 99%

The promiscuous evolutionary history of the family Bromoviridae

Codoñer

Elena

2008

Journal of General Virology

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Recombination and segment reassortment are important contributors to the standing genetic variation of RNA viruses and are often involved in the genesis of new, emerging viruses. This study explored the role played by these two processes in the evolutionary radiation of the plant virus family Bromoviridae. The evolutionary history of this family has been explored previously using standard molecular phylogenetic methods, but incongruences have been found among the trees inferred from different gene sequences. This would not be surprising if RNA exchange was a common event, as it is well known that recombination and reassortment of genomes are poorly described by standard phylogenetic methods. In an attempt to reconcile these discrepancies, this study first explored the extent of segment reassortment and found that it was common at the origin of the bromoviruses and cucumoviruses and at least at the origin of alfalfa mosaic virus, American plum line pattern virus and citrus leaf rugose virus. Secondly, recombination analyses were performed on each of the three genomic RNAs and it was found that recombination was very common in members of the genera Bromovirus, Cucumovirus and Ilarvirus. Several cases of recombination involving species from different genera were also identified. Finally, a phylogenetic network was constructed reflecting these genetic exchanges. The network confirmed the taxonomic status of the different genera within the family, despite the phylogenetic noise introduced by genetic exchange. INTRODUCTIONRecombination and segment reassortment are important mechanisms for the genesis of new genetic variability in RNA virus populations. Proportionally, the amount of genetic variability produced after a single recombination event is larger than that produced by single point mutations. Although the importance of recombination was underappreciated in early studies of virus genome evolution, it is now recognized as a widespread phenomenon among positive-strand RNA viruses in animals (Grassly & Holmes, 1997;Holmes et al., 1999;Wilson et al., 1988) and plants (Nagy & Bujarski, 1993;Revers et al., 1996;Aranda et al., 1997;Olsthoorn et al., 2002;Bousalem et al., 2003;Cheng & Nagy, 2003;Moreno et al., 2004;Tan et al., 2004;Bonnet et al., 2005;Urbanowicz et al., 2005;Chare & Holmes, 2006;Weng et al., 2007), as well as in retroviruses such as human immunodeficiency virus type 1 Prljic et al., 2004;Althaus & Bonhoeffer, 2005;Galetto & Negroni, 2005), although it is a rare or even non-existent phenomenon among negativestrand viruses (Chare et al., 2003). There are several mechanisms by which RNA recombination may take place, the most common of which is homologous recombination (Lai, 1992). During this process, the donor replaces a highly homologous region in the acceptor, with the recombinant retaining exactly the same genomic organization of the parental RNA molecules. Therefore, the term homologous refers not only to the presence of sequence homology between both parental RNAs but also the necessity of homologous...

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Phylogenetic analysis reveals a low rate of homologous recombination in negative-sense RNA viruses

Cited by 253 publications

References 61 publications

Isolates of Zaire ebolavirus from wild apes reveal genetic lineage and recombinants

Isolates of Zaire ebolavirus from wild apes reveal genetic lineage and recombinants

Density-Dependent Selection in Vesicular Stomatitis Virus

The promiscuous evolutionary history of the family Bromoviridae

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