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Monitoring sequence space as a test for the target of selection in viruses.

Abstract：

:An essential feature of viral quasispecies, predicted from quasispecies theory, is that the target of selection is the mutant distribution as a whole. To test molecularly the mutant composition selected from a viral quasispecies we reconstructed a mutant distribution using 19 antigenic variants of foot-and-mouth disease virus (FMDV). Each variant was marked by a specific amino acid replacement at a major antigenic site of the virus that conferred resistance to a monoclonal antibody (mAb). The variants were introduced in the mutant spectrum of a biological FMDV clone, at a frequency commonly found in FMDV quasispecies. The reconstructed quasispecies (and a number of control populations) were allowed to replicate in the presence or absence of the mAb. The mutant distribution that became dominant as a result of antibody selection included at least ten of the 19 mutants initially used to reconstruct the quasispecies. No such biased mutant repertoire was found in control populations. The results show that a mutant distribution was selected, and are incompatible with selection of an individual genome, which then generated multiple mutants upon further replication. An ample representation of variants immediately following a selection event should contribute to subsequent adaptability of the virus.

journal_name

J Mol Biol

journal_title

Journal of molecular biology

authors

Perales C,Martín V,Ruiz-Jarabo CM,Domingo E

doi

10.1016/j.jmb.2004.10.066

keywords:

subject

Has Abstract

pub_date

2005-01-21 00:00:00

pages

451-9

issue

3

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(04)01372-5

journal_volume

345

pub_type

杂志文章

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