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- Bordería, Antonio V, et al.
(author)
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Group Selection and Contribution of Minority Variants during Virus Adaptation Determines Virus Fitness and Phenotype.
- 2015
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In: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 11:5
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Journal article (peer-reviewed)abstract
- Understanding how a pathogen colonizes and adapts to a new host environment is a primary aim in studying emerging infectious diseases. Adaptive mutations arise among the thousands of variants generated during RNA virus infection, and identifying these variants will shed light onto how changes in tropism and species jumps can occur. Here, we adapted Coxsackie virus B3 to a highly permissive and less permissive environment. Using deep sequencing and bioinformatics, we identified a multi-step adaptive process to adaptation involving residues in the receptor footprints that correlated with receptor availability and with increase in virus fitness in an environment-specific manner. We show that adaptation occurs by selection of a dominant mutation followed by group selection of minority variants that together, confer the fitness increase observed in the population, rather than selection of a single dominant genotype.
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3. |
- Rodriguez-Roche, Rosmari, et al.
(author)
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Increasing clinical severity during a dengue virus type 3 Cuban epidemic: deep sequencing of evolving viral populations
- 2016
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In: Journal of Virology. - 1098-5514. ; 90:19, s. 4320-4333
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Journal article (peer-reviewed)abstract
- During the DENV-3 epidemic occurred in Havana in 2001-2002, severe disease was associated with the infection sequence DENV-1/DENV-3, whilst the sequence DENV-2/DENV-3 was associated with mild/asymptomatic infections. To determine the role of the virus in the increasing severity demonstrated during the epidemic serum samples collected at different point times were studied. A total of 22 full-length sequences were obtained using a deep sequencing approach. Bayesian phylogenetic analysis of consensus sequences revealed that two DENV-3 lineages were circulating in Havana at that time, both grouped within genotype III. The predominant lineage is closely related to Peruvian and Ecuadorian strains, whilst the minor lineage is related to Venezuelan strains. According to consensus sequences, relatively few non-synonymous mutations were observed; only one was fixed during the epidemic at position 4380 in the NS2B gene. Intra-host genetic analysis indicated that a significant minor population was selected and became predominant towards the end of the epidemic. In conclusion, greater variability was detected during the epidemic's progression in terms of significant minority variants, particularly in the non-structural genes. An increasing trend of genetic diversity towards the end of the epidemic was only observed for synonymous variant allele rates, with higher variability in secondary cases. Remarkably, significant intra-host genetic variation was demonstrated within the same patient during the course of secondary infection DENV-1/DENV-3, including changes in the structural proteins PrM and E. Therefore, the dynamic of evolving viral populations in the context of heterotypic antibodies could be related to the increasing clinical severity observed during the epidemic.
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