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Review
. 2019 Jan 7:114:e180251.
doi: 10.1590/0074-02760180251.

Origin, tempo, and mode of the spread of DENV-4 Genotype IIB across the state of São Paulo, Brazil during the 2012-2013 outbreak

Ayda Susana Ortiz-Baez  1 , Marielton Dos Passos Cunha  1 , Danila Vedovello  2 , Tatiana Elias Colombo  3 , Maurício Lacerda Nogueira  3 , Christian Julián Villabona-Arenas  4   5 , Paolo Marinho de Andrade Zanotto  1
Affiliations
Review

Origin, tempo, and mode of the spread of DENV-4 Genotype IIB across the state of São Paulo, Brazil during the 2012-2013 outbreak

Ayda Susana Ortiz-Baez et al. Mem Inst Oswaldo Cruz. .

Abstract

Background: Dengue virus type 4 (DENV-4) was first reported in Brazil in 1982 and since then no more cases were detected again in Brazil until 2010, when the virus was reintroduced. Over the following years, the virus spread to several Brazilian states and resulted in about 1,400,000 dengue cases, in 2013. The largest number of cases were documented in the Southeast macro-region.

Objectives: To determine the phylogeography of DENV-4 Genotype IIB strains isolated during the epidemics in 2012-2013 in São Paulo, Brazil, we aimed to contextualise the contribution of viruses sampled in different localities across the overall movement of DENV-4 in Brazil.

Methods: Based on the envelope gene sequences retrieved from GenBank, we employed a Bayesian phylogeographic approach to assess the spatiotemporal dynamics of DENV-4 Genotype IIB in São Paulo, Brazil.

Findings: The dispersal dynamics of DENV-4 Genotype IIB in Brazil indicated Rio de Janeiro and Mato Grosso states as the most likely routes toward São Paulo before the 2012-2013 outbreak. Likewise, Guarujá and São José do Rio Preto facilitated viral spread and transmission to other localities in the South and Southeast macro-regions in Brazil.

Conclusions: The spread pattern of DENV-4 Genotype IIB strains across the country supports two independent introductions of the virus in São Paulo in a short period of time. Furthermore, São Paulo appears to have played a pivotal role in the dissemination of DENV-4 to other locations in Brazil.

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Figures

Fig. 1:
Fig. 1:. maximum likelihood phylogenetic tree of dengue virus type 4 (DENV-4) based on full-length envelope gene sequences (n = 1408). (A) DENV-4 genotypes. (B) Clustering of Brazilian sequences in lineages I-III. Location acronyms: Amazonas (AM); Minas Gerais (MG); Mato Grosso (MT); Pará (PA); Paraná (PR); Rio de Janeiro (RJ); Roraima (RR); São Paulo (SP).
Fig. 2:
Fig. 2:. correlation between genetic divergence and sampling time from root-to-tip distances using dengue virus type 4 (DENV-4) sequences. Root-to-tip distances were inferred using a maximum likelihood phylogeny for DAT-1 (A) and DAT-2 (B).
Fig. 3:
Fig. 3:. bayesian discrete phylogeography of genotype IIB dengue virus type 4 (DENV-4) strains (DAT-1). Maximum clade credibility (MCC) phylogeny inferred using envelope sequences. Brazilian sequences are grouped in three lineages designated as Lineage I-III. The DENV-4 strain from São Paulo state is indicated with an asterisk. The size of node circle is proportionate to the posterior probability of the node. Nodes with yellow circles have a support > 0.9. Branches are coloured according to the most probably ancestral lineage location.
Fig. 4:
Fig. 4:. bayesian discrete phylogeography of Brazilian dengue virus type 4 (DENV-4) strains (DAT-2). (A) Maximum clade credibility (MCC) phylogeny inferred using envelope sequences. The designated lineage identity in Fig. 2 was maintained. DENV-4 strains from São Paulo state are indicated with asterisks. The size of node circle is proportionate to the posterior probability of the node. Nodes with yellow circles have a support > 0.9. Branches are coloured according to the most probable location of the ancestral lineage. (B) Bayesian skyride reconstruction showing population size fluctuations of DENV-4 in Brazil. The dotted dash line represents the median estimate and the shaded area shows the 95% credibility interval. Location acronyms: Amazonas, Manaus (BRAMMA); Minas Gerais, Divinópolis (BRMGDV); Mato Grosso, Cuiabá (BRMTCU); Mato Grosso, Nossa Senhora do Livramento (BRMTNL); Mato Grosso, Poconé (BRMTPO); Mato Grosso, Várzea Grande (BRMTVG); Paraná, Cambé (BRPRCA); Rio de Janeiro, Rio de Janeiro (BRRJRJ); Roraima, Boa Vista (BRRRBV); São Paulo, Guarujá (BRSPGU); São Paulo, São José do Rio Preto (BRSPSJ).
Fig. 5:
Fig. 5:. phylogeographic diffusion of dengue virus type 4 (DENV-4) across Brazil (DAT-2). (A) Spatial projection of the MCC tree. The grey lines represent branches connecting geographic locations. Numbers allow identifying the temporal order of diffusion events. The dotted dashed circle indicates the presence of several diffusion paths within Mato Grosso state, which are not exhibited here. (B) Spatial visualisation of significant non-zero rates using Bayes factor test (BF > 3). The line colour indicates the statistical support for each rate, weak (bright red) and strong (dark red). Arrows next to lines with upward and downward curvatures depict westward and eastward movements. Brazilian states are coloured by geographic macro-region. Location acronyms: Amazonas, Manaus (BRAMMA); Minas Gerais, Divinópolis (BRMGDV); Mato Grosso, Cuiabá (BRMTCU); Mato Grosso, Nossa Senhora do Livramento (BRMTNL); Mato Grosso, Poconé (BRMTPO); Mato Grosso, Várzea Grande (BRMTVG); Paraná, Cambé (BRPRCA); Rio de Janeiro, Rio de Janeiro (BRRJRJ); Roraima, Boa Vista (BRRRBV); São Paulo, Guarujá (BRSPGU); São Paulo, São José do Rio Preto (BRSPSJ).
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