Transmission bottlenecks as determinants of virulence in rapidly evolving pathogens

Bergstrom, Carl T.; McElhany, Paul; Real, Leslie A.

doi:10.1073/pnas.96.9.5095

Cited by 160 publications

(141 citation statements)

References 35 publications

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“…In this sense, the occurrence of bottlenecks can be decisive to avoid extinction by aiding to isolate genomes that are able to initiate an infection (25,26). From this point of view, bottleneck events would be a kind of positive selection operating against extinction caused by increases in the mutation rate.…”

Section: Discussionmentioning

confidence: 99%

Suppression of viral infectivity through lethal defection

Grande-Pérez

Lázaro

Löwenstein

et al. 2005

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

172

212

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RNA viruses replicate with a very high error rate and give rise to heterogeneous, highly plastic populations able to adapt very rapidly to changing environments. Viral diseases are thus difficult to control because of the appearance of drug-resistant mutants, and it becomes essential to seek mechanisms able to force the extinction of the quasispecies before adaptation emerges. An alternative to the use of conventional drugs consists in increasing the replication error rate through the use of mutagens. Here, we report about persistent infections of lymphocytic choriomeningitis virus treated with fluorouracil, where a progressive debilitation of infectivity leading to eventual extinction occurs. The transition to extinction is accompanied by the production of large amounts of RNA, indicating that the replicative ability of the quasispecies is not strongly impaired by the mutagen. By means of experimental and theoretical approaches, we propose that a fraction of the RNA molecules synthesized can behave as a defective subpopulation able to drive the viable class extinct. Our results lead to the identification of two extinction pathways, one at high amounts of mutagen, where the quasispecies completely loses its ability to infect and replicate, and a second one, at lower amounts of mutagen, where replication continues while the infective class gets extinct because of the action of defectors. The results bear on a potential application of increased mutagenesis as an antiviral strategy in that low doses of a mutagenic agent may suffice to drive persistent virus to extinction.error catastrophe ͉ mutagen ͉ RNA virus ͉ replicative ability ͉ mathematical model

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Section: Discussionmentioning

confidence: 99%

Suppression of viral infectivity through lethal defection

Grande-Pérez

Lázaro

Löwenstein

et al. 2005

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

172

212

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“…We show here that, in addition to genetic drift experienced by viral populations within plant hosts, extremely narrow bottlenecks also shape plant virus populations during nonpersistent aphid transmission. These repeated and narrow bottlenecks during virus epidemics may have several important consequences on virus evolution, such as decreases of fitness (18,19), of (broad-sense) virulence (20), and of the capacity to respond to natural selection (21) and could also contribute to the differentiation of plant virus populations at the field or regional scales. Also, the quasi-species model of viruses, which assumes an absence of genetic drift during the evolution of virus populations, could be irrelevant for some plant viruses because of the drastic effect of bottlenecks (22).…”

Section: Discussionmentioning

confidence: 99%

Estimation of the number of virus particles transmitted by an insect vector

Moury¹,

Fabre²,

Senoussi

2007

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

147

116

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Plant viruses are submitted to narrow population bottlenecks both during infection of their hosts and during horizontal transmission between host individuals. The size of bottlenecks exerted on virus populations during plant invasion has been estimated in a few pathosystems but is not addressed yet for horizontal transmission. Using competition for aphid transmission between two Potato virus Y variants, one of them being noninfectious but equally transmissible, we obtained estimates of the size of bottlenecks exerted on an insect-borne virus during its horizontal transmission. We found that an aphid transmitted on average 0.5-3.2 virus particles, which is extremely low compared with the census viral population into a plant. Such narrow bottlenecks emphasize the strength of stochastic events acting on virus populations, and we illustrate, in modeling virus emergence, why estimating this parameter is important.aphid ͉ genetic drift ͉ population bottleneck ͉ potyvirus ͉ nonpersistent virus

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“…Transmission bottlenecks are one important case in which the size of microbial populations undergoes extreme changes. A number of studies have considered the impact of bottlenecks for the evolution of pathogens (Bergstrom et al 1999;Wahl and Gerrish 2001;Wahl et al 2002;Manrubia et al 2005;Escarmis et al 2006). Those studies focus on mutants that have a different fitness as measured by the effective growth rate.…”

Section: Discussionmentioning

confidence: 99%

Surviving the Bottleneck: Transmission Mutants and the Evolution of Microbial Populations

Handel

Bennett

2008

Genetics

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The ability of microbial populations to increase fitness through fixation of mutants with an increased growth rate has been well described. In experimental studies, this is often the only way fitness can be increased. In natural settings, however, fitness can also be improved by increasing the ability of the microbe to transmit from one host to the next. For many pathogens, transmission includes a phase outside the host during which they need to survive before the chance of reinfecting a new host occurs. In such a situation, a reduced death rate during this phase will lead to improved fitness. Here, we compute the fixation probability of mutants that better survive the transmission bottleneck during the evolution of microbial populations. We derive analytical results that show that transmission mutants are often likely to occur and that their importance relative to growth mutants increases as the population decline during the transmission phase increases. We confirm our theoretical results with numerical simulations and suggest specific experiments that can be done to test our predictions.

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Transmission bottlenecks as determinants of virulence in rapidly evolving pathogens

Cited by 160 publications

References 35 publications

Suppression of viral infectivity through lethal defection

Suppression of viral infectivity through lethal defection

Estimation of the number of virus particles transmitted by an insect vector

Surviving the Bottleneck: Transmission Mutants and the Evolution of Microbial Populations

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