Origen, Evolución y Clasificación de los Virus: Quasispecies y Estructura - Prof. Gironès, Apuntes de Virología

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Rosina Girones

TEMA 2. ESTRUCTURA Y EVOLUCIÓN DE LOS

VIRUS

Í N D I C E

Origen i evolució dels virus

Estructura, morfologia i composició química

The Tree of Life Web Project (ToL) is a collaborative effort of biologists and nature enthusiasts from around the world. On more than 10, World Wide Web pages, the project provides information about biodiversity, the characteristics of different groups of organisms, and their evolutionary history (phylogeny).

O R I G E N Y E V O L U C I Ó N D E L O S V I R U S

Viruses are obligate parasites of Eukarya, Archaea and Bacteria.

The rooting of the Tree of Life, and the relationships of the major

lineages, are controversial. The monophyly of Archaea is uncertain,

and recent evidence for ancient lateral transfers of genes indicates

that a highly complex model is needed to adequately represent the

phylogenetic relationships among the major lineages of Life.

Los virus, en los estudios evolutivos, aunque es conocida su importancia a nivel de la evolución, quedan a parte y no esta todavía definido su papel

O R I G E N Y E V O L U C I Ó N D E L O S V I R U S.

From RNA world to DNA world. Forterre proposes that all living organisms share a common ancestor that stored its genetic information in RNA. Some of its genes evolved into viruses. Later, some of those viruses evolved DNA as a way to defend their genes from attack, and DNA-based viruses became incorporated into hosts. Host genes were then transferred onto viral chromosomes and shared. In the process, the three major domains of DNA-based life emerged. Ref. Science 2006: Vol. 312 no. 5775 pp. 870-872 DOI: 10.1126/science.312.5775.870****. News. Did DNA Come From Viruses? Carl Zimmer

The ranges of substitution rates for coding sequences of viruses with different genomic architectures. Substitution rates are given as substitutions per site per year on a logarithmic scale. Data for viruses from Fields Virology with updates. The red circle indicates the average value for mammalian nuclear coding sequences. Ref. Are viruses a source of new protein folds for organisms? – Virosphere structure space and evolution. A. Abroi and J. Gough. Bioessays 00: 000–000, 2011 WILEY Periodicals, Inc. www.bioessays-journal.com. DOI 10.1002/bies.

O R I G E N Y E V O L U C I Ó N D E L O S V I R U S

Factores importantes de variabilidad genética:

 Fidelidad de la replicación del genoma ( tipo de polimerasa)

 Tasa de replicación

 Tamaño de la población ( tanto del virus como del huésped)

 Mecanismos de transmisión

 Frecuencia y huéspedes en que se producen coinfecciones

Mecanismos moleculares de generación de variabilidad genética:

1. Mutaciones
2. Recombinaciones
3. Reassortment ( reagrupamientos)

M E C A N I S M O S D E D I V E R S I F I C A C I Ó N G E N É T I C A D E L O S V I R U S

O R I G E N Y E V O L U C I Ó N D E L O S V I R U S

2. Recombinaciones

• Intercambio de material genético entre 2 cadenas de ácido nucleico (DNA o RNA).
• Puede producirse a diferentes niveles:
• Virus con la célula huésped
• Entre 2 virus diferentes
  • implica confección de una misma célula
  • cepas víricas, especies, géneros...
• Tiene como resultado cambios evolutivos drásticos y rápidos.

O R I G E N Y E V O L U C I Ó N D E L O S V I R U S

2. Reassortment (reagrupamientos)

• Virus con genomas segmentados (o diploides)
• Coinfección de 2 virus diferentes en una misma célula
• Ejemplo: virus de la gripe: Antigenic shift ( canvio antigénico)

 The quasispecies theory predicts that viruses are not just a

collection of random mutants, but an interactive group of

variants. Diversity of the population is critical for propagation of

the viral infection. Recently it became experimentally feasible to

test the idea that viral populations, not individual mutants, are

the target of selection.

Q U A S I S P E C I E S

 The consequence of a quasispecies is that most viral

infections are initiated not by a single virion, but a

population of particles. The progeny produced after this

infection results from selective forces that operate

inside the infected host. The virions that go on to infect

a new host have passed through another set of external

selective forces. A steady-state population of a viral

quasispecies consists of a vast number of particles.

 The diagram shows a small subset of the viral genomes

that are present in a virus stock. Genomes are indicated

by lines, and mutations are shown by different symbols.

The consensus sequence for this population is shown as

a line at the bottom. There are no mutations in the

consensus sequence, even though every viral genome

contains mutations. This is because no mutation is

present at sufficiently high levels to achieve a

consensus at any position.

Q U A S I S P E C I E S

A virus replicating with a high mutation rate will generate a diverse mutant repertoire over the course of a few generations.

In these trees, each branch indicates two variants linked by a point mutation and the concentric circles represent serial replication cycles. The resulting distribution is often represented as a cloud centered on a master sequence.

This two dimensional schematic is a vast oversimplification of the intraquasispecies connectivity. In the mathematical formulations of quasispecies theory, sequence space is multidimensional, with numerous branches between variants.

Q U A S I S P E C I E S

Q U A S I S P E C I E S

Dinámica de quasiespecies víricas: fitness y bottlenecks (cuellos

de botella)

Fitness: Habilidad relativa de producir progenie estable

infecciosa en un ambiente determinado. En un ambiente

constante y en poblaciones grandes se gana en fitness

Cuellos de botella → pérdida de fitness de la población y

acumulación de mutaciones deletéreas. Un “bottleneck” puede

impedir el establecimiento de una infección.

Cuellos de botella naturales:

Transmisión por aerosoles

Activación de un provirus

Transmisión mamíferos ↔ artrópodos

Transmisión fecal-oral

Q U A S I S P E C I E S

The diagram on the left shows a small subset of the viral genomes that are present in a virus stock.

• Genomes are indicated by lines, and mutations are shown by different symbols.
• The consensus sequence for this population is shown as a line at the bottom.
• There are no mutations in the consensus sequence, even though every viral genome contains mutations.
• One of these genomes, indicated by the arrow, is able to survive a selection event (also called a genetic bottleneck ), such as passage to a new host.
• This virus multiplies in the host and a new population of viruses emerges, shown by the diagram on the right.
• The consensus sequence for this population indicates that three mutations selected to survive the bottleneck are found in every member of the population.
• Error-prone replication ensures that the members of the new population have many other mutations in their genomes.

 Population diversity is a virulence determinant.

Results of experiments described in Vignuzzi et al. A neurovirulent clone of poliovirus was isolated from the brains of mice that had been infected with a wild-type strain. Naive mice were then reinfected with this clone as part of either a genetically constrained (top) or diverse population (bottom).

Although all mice received the neurovirulent clone, only those infected with a diverse quasispecies developed disease. Subpopulations within the diverse quasispecies cooperated with the neurovirulent clone to facilitate its entry into the CNS.

Vignuzzi M, Stone JK, Arnold JJ, Cameron CE, Andino R (2006) Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population. Nature 439: 344– 348.

Q U A S I S P E C I E S