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. 2013 Aug 2;8(8):e70318.
doi: 10.1371/journal.pone.0070318. Print 2013.

Inter- and intra-host viral diversity in a large seasonal DENV2 outbreak

Camila Malta Romano  1 , Michael Lauck, Felipe S Salvador, Célia Rodrigues Lima, Lucy S Villas-Boas, Evaldo Stanislau A Araújo, José Eduardo Levi, Claudio Sergio Pannuti, David O'Connor, Esper Georges Kallas
Affiliations

Inter- and intra-host viral diversity in a large seasonal DENV2 outbreak

Camila Malta Romano et al. PLoS One. .

Abstract

Background: High genetic diversity at both inter- and intra-host level are hallmarks of RNA viruses due to the error-prone nature of their genome replication. Several groups have evaluated the extent of viral variability using different RNA virus deep sequencing methods. Although much of this effort has been dedicated to pathogens that cause chronic infections in humans, few studies investigated arthropod-borne, acute viral infections.

Methods and principal findings: We deep sequenced the complete genome of ten DENV2 isolates from representative classical and severe cases sampled in a large outbreak in Brazil using two different approaches. Analysis of the consensus genomes confirmed the larger extent of the 2010 epidemic in comparison to a previous epidemic caused by the same viruses in another city two years before (genetic distance = 0.002 and 0.0008 respectively). Analysis of viral populations within the host revealed a high level of conservation. After excluding homopolymer regions of 454/Roche generated sequences, we found 10 to 44 variable sites per genome population at a frequency of >1%, resulting in very low intra-host genetic diversity. While up to 60% of all variable sites at intra-host level were non-synonymous changes, only 10% of inter-host variability resulted from non-synonymous mutations, indicative of purifying selection at the population level.

Conclusions and significance: Despite the error-prone nature of RNA-dependent RNA-polymerase, dengue viruses maintain low levels of intra-host variability.

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Conflict of interest statement

Competing Interests: The authors state that the co-author Dr Esper George Kallas is currently a PLOS ONE Editorial Board member and also declare that this does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Geographic region of 2010 Santos epidemic.
Southern São Paulo coastal region where viruses from this study were sampled are in red in the São Paulo map. Full black and red circles in the region focused represent the cities affected. The size of the circles specifies the magnitude of the epidemic in each city, also given by the number of reported cases in Santos (St), Praia Grande (PG), Guarujá (Gu), São Vicente (SV) and Cubatão (Cu).
Figure 2
Figure 2. Inter-host variability.
A- The line graph summarizes the level of accumulated variability per genome region across the Santos consensus viruses. B- Variability (synonymous changes) among consensus sequences sampled in Santos (light blue squares) compared to the variability among viruses from previous epidemics in 2008 in Ribeirão Preto, SP (green squares). Non-synonymous changes are represented in dark blue in both populations.
Figure 3
Figure 3. Bayesian phylogenetic tree of 124 DENV2 complete genomes.
A-The tree shows the eleven Brazilian viruses sequenced in this study (two-color highlighted cluster at the top) and globally sampled DENV2 genomes. Blue branches represent Brazilian viruses sampled in previous epidemics. Posterior probability of all key nodes is depicted. B- Clusters of viruses sequenced during this study. The blue bar in the branch leading to clade 2 represents the amino acid change at position T180I in envelope gene.
See this image and copyright information in PMC

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