Our systems are now restored following recent technical disruption, and we’re working hard to catch up on publishing. We apologise for the inconvenience caused. Find out more: https://www.cambridge.org/universitypress/about-us/news-and-blogs/cambridge-university-press-publishing-update-following-technical-disruption
We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure coreplatform@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Virology has undergone a profound transformation with the incorporation of quasispecies theory to the understanding of the composition and dynamics of viral populations as they cause disease. RNA viral populations do not consist of a genome class with a defined nucleotide sequence but of a cloud or swarm or related mutants due to high mutation rates (number of incorrect nucleotides introduced per nucleotide copied) during replication. DNA and RNA viruses whose multiplication is catalysed by a low fidelity polymerase replicate close to an error threshold for maintenance of their genetic information. This means that modest increases in mutation rate jeopardize their genetic stability. Realization of this important corollary of quasispecies theory has opened new approaches to combating viral disease. One of these approaches is lethal mutagenesis that consists of forcing virus extinction by an excess of mutations evoked by virus-specific mutagenic agents. This article summarizes the origin and current status of this new antiviral approach.
The 1918 Spanish influenza is one of the most dramatic examples of the unpredictable threat that viral epidemics represent for the human population. In the words of Joshua Lederberg, “The survival of the human species is not a preordained evolutionary program. Abundant resources of genetic variation exist for viruses to learn new tricks, not necessarily confined to what happens routinely or even frequently.” Since 1918 we have learned about the nature of viruses, their structure, their replication in intimate relationship with their host cells and organisms, and their mechanisms of evolutionary change. Concerning the “tricks” mentioned by Lederberg, we have learned that influenza viruses can use a very large repertoire.
RNA viruses are replicated by RNA-dependent RNA (or DNA) polymerases (also termed “reverse transcriptases”), which tend to introduce incorrect nucleotides during template copying. The incorrect nucleotides are perpetuated in the genetic material of the viruses, unless the mistakes are corrected (by repair enzymes), or the genomes harboring them are eliminated by a process termed negative selection (as opposed to positive or Darwinian selection). The reason for this error-prone replication is that most viral polymerases lack an activity of error correction that is termed proofreadingrepair activity. This is in contrast to cellular DNA polymerases (and some viral DNA polymerases) involved in DNA replication, which include such a correcting function. Other repair activities in the cell that can eliminate errors in DNA are not active on replicating RNA viruses. Mistakes during viral RNA replication average one misincorporation for every ten thousand nucleotides incorporated during template copying (fig. 1.1, pt. A).
In addition to mutation, most RNA viruses can also undergo genetic recombination, a process by which a mosaic genome can be produced from two different parents. Mutation and recombination give rise to complex and dynamic mutant distributions termed “viral quasispecies” (fig. 1.1, pt. B). Quasispecies dynamics provides a mechanism for the adaptability of RNA viruses. Fitness gains can be regarded as an optimization of mutant distributions. This view is supported by many experiments that have established that competitive replication in a given environment leads to fitness gain in that same environment, while the forced accumulation of mutations (naturally through population bottlenecks or artificially with mutagenic agents) leads to fitness loss.
The Spanish Influenza Pandemic of 1918-1919 sheds new light on what the World Health Organization described as "the single most devastating infectious disease outbreak ever recorded" by situating the Iberian Peninsula as the key point of connection, both epidemiologically and discursively, between Europe and the Americas. The essays in this volume elucidate specific aspects of the pandemic that have received minimal attention until now, including social control, gender, class, religion, national identity, and military medicine's reactions to the pandemic and its relationship with civilian medicine, all in the context of World War I. As the authors point out, however, the experiences of 1918-19 remain persistently relevant to contemporary life, particularly in view of events such as the 2009 H1N1 swine flu pandemic. Contributors: Mercedes Pascual Artiaga, Catherine Belling, Josep Bernabeu-Mestre, Ryan A, Davis, Esteban Domingo, Magda Fahrni, Hernán Feldman, Pilar León-Sanz, Maria Luísa Lima, Maria deFátima Nunes, María-Isabel Porras-Gallo, Anny Jackeline Torres Silveira, José Manuel Sobral, Paulo Silveira e Sousa, Christiane Maria Cruz de Souza. María-Isabel Porras-Gallo is Professor of History of Science in the Medical Faculty of Ciudad Real at the University of Castile-La Mancha (Spain). She is the author of Un reto para la sociedad madrileña: la epidemia de gripe de 1918-1919 and co-editor of El drama de la polio. Un problema social y familiar en la España franquista. Ryan A. Davis is Assistant Professor in the Department of Languages, Literatures, and Cultures at Illinois State University. He is the author of The Spanish Flu: Narrative and Cultural Identity in Spain, 1918.