Worldwide spread of Dengue virus type 1

BACKGROUND:\ud DENV-1 is one of the four viral serotypes that causes Dengue, the most common mosquito-borne viral disease of humans. The prevalence of these viruses has grown in recent decades and is now present in more than 100 countries. Limited studies document the spread of DENV-1 over the world despite its importance for human health.\ud \ud METHODOLOGY/PRINCIPAL FINDINGS:\ud We used representative DENV-1 envelope gene sequences to unravel the dynamics of viral diffusion under a Bayesian phylogeographic approach. Data included strains from 45 distinct geographic locations isolated from 1944 to 2009. The estimated mean rate of nucleotide substitution was 6.56 × 10⁻⁴ substitutions/site/year. The larger genotypes (I, IV and V) had a distinctive phylogenetic structure and since 1990 they experienced effective population size oscillations. Thailand and Indonesia represented the main sources of strains for neighboring countries. Besides, Asia broadcast lineages into the Americas and the Pacific region that diverged in isolation. Also, a transmission network analysis revealed the pivotal role of Indochina in the global diffusion of DENV-1 and of the Caribbean in the diffusion over the Americas.\ud \ud CONCLUSIONS/SIGNIFICANCE:\ud The study summarizes the spatiotemporal DENV-1 worldwide spread that may help disease control.FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, 2010/19059-7)FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo, 2011/17071-2)CNP

The Challenges Imposed by Dengue, Zika, and Chikungunya to Brazil

Brazil has a well-established immunization program in which vaccines are provided through the Public Health System free of charge to the whole population, obtaining high coverage and reducing the incidence of important infectious diseases in children and adults. However, the environmental changes and high mobility rates of the population occurring in the last decades have triggered the sequential introduction of a series of vector-borne emerging infectious diseases, such as Dengue, Zika, and Chikungunya, that have imposed a considerable burden on the population, with yet unmet solutions. The first to be introduced in Brazil was the Dengue virus, reaching epidemic levels in 2010, with over 1 million cases annually, maintaining high infection rates until 2016. Brazil has invested in vaccine development. The Zika virus infection, initially assumed to have appeared during the World Cup in 2014, was later shown to have arrived earlier in 2013. Its emergence mobilized the Brazilian scientific community to define priorities and strategies, that rapidly investigated mechanisms of pathogenesis, differential diagnostics, and determined that Zika virus infection per se causes relatively mild symptoms, however, in pregnant women can cause microcephaly in the newborns. The diagnostics of Zika infection is confusing given its similar symptoms and cross-reactivity with Dengue, which also hindered the appraisal of the extent of the epidemics, which peaked in 2015 and finished in 2016. Another complicating factor was the overlap with Chikungunya virus infection, which arrived in Brazil in 2014, being prevalent in the same regions, with similar symptoms to both Dengue and Zika. Although Dengue infection can be fatal and Zika infection in pregnant woman can lead to newborns with microcephaly or an array of neurodegenerative manifestations, the Chikungunya infection is a debilitating disease leaving chronic sequelae, which unfortunately has received less attention. Precise differential diagnostics of Dengue, Zika, and Chikungunya will be necessary to evaluate the actual extent of each of these diseases during this overlapping period. Here we review the impact of these emerging infections on public health and how the scientific community was mobilized to deal with them in Brazil

Phylodynamics and Dispersal of HRSV Entails Its Permanence in the General Population in between Yearly Outbreaks in Children

Background: Human respiratory syncytial virus (HRSV) is one of the major etiologic agents of respiratory tract infections among children worldwide. Methodology/Principal Findings: Here through a comprehensive analysis of the two major HRSV groups A and B (n = 1983) which comprise of several genotypes, we present a complex pattern of population dynamics of HRSV over a time period of 50 years (1956-2006). Circulation pattern of HRSV revealed a series of expansions and fluctuations of co-circulating lineages with a predominance of HRSVA. Positively selected amino acid substitutions of the G glycoprotein occurred upon population growth of GB3 with a 60-nucleotide insertion (GB3 Insert), while other genotypes acquired substitutions upon both population growth and decrease, thus possibly reflecting a role for immune selected epitopes in linkage to the traced substitution sites that may have important relevance for vaccine design. Analysis evidenced the co-circulation and predominance of distinct HRSV genotypes in Brazil and suggested a year-round presence of the virus. In Brazil, GA2 and GA5 were the main culprits of HRSV outbreaks until recently, when the GB3 Insert became highly prevalent. Using Bayesian methods, we determined the dispersal patterns of genotypes through several inferred migratory routes. Conclusions/Significance: Genotypes spread across continents and between neighboring areas. Crucially, genotypes also remained at any given region for extended periods, independent of seasonal outbreaks possibly maintained by re-infecting the general population.FAPESPFAPESP [Nu 00/4205-6

Modularity and evolutionary constraints in a baculovirus gene regulatory network

Abstract\ud \ud \ud \ud Background\ud The structure of regulatory networks remains an open question in our understanding of complex biological systems. Interactions during complete viral life cycles present unique opportunities to understand how host-parasite network take shape and behave. The Anticarsia gemmatalis multiple nucleopolyhedrovirus (AgMNPV) is a large double-stranded DNA virus, whose genome may encode for 152 open reading frames (ORFs). Here we present the analysis of the ordered cascade of the AgMNPV gene expression.\ud \ud \ud \ud Results\ud We observed an earlier onset of the expression than previously reported for other baculoviruses, especially for genes involved in DNA replication. Most ORFs were expressed at higher levels in a more permissive host cell line. Genes with more than one copy in the genome had distinct expression profiles, which could indicate the acquisition of new functionalities. The transcription gene regulatory network (GRN) for 149 ORFs had a modular topology comprising five communities of highly interconnected nodes that separated key genes that are functionally related on different communities, possibly maximizing redundancy and GRN robustness by compartmentalization of important functions. Core conserved functions showed expression synchronicity, distinct GRN features and significantly less genetic diversity, consistent with evolutionary constraints imposed in key elements of biological systems. This reduced genetic diversity also had a positive correlation with the importance of the gene in our estimated GRN, supporting a relationship between phylogenetic data of baculovirus genes and network features inferred from expression data. We also observed that gene arrangement in overlapping transcripts was conserved among related baculoviruses, suggesting a principle of genome organization.\ud \ud \ud \ud Conclusions\ud Albeit with a reduced number of nodes (149), the AgMNPV GRN had a topology and key characteristics similar to those observed in complex cellular organisms, which indicates that modularity may be a general feature of biological gene regulatory networks.JVCO, CTB and AI hold FAPESP scholarships (04/12456-0, 09/16740-8 and 12/04818-5), AFB and CCMF hold CAPES-MSc and PhD scholarships and PMAZ holds a CNPq-PQ scholarship. This work was supported financially by FAPESP (Fundação de Amparo a Pesquisa do Estado de São Paulo, process: 2007/55282-0)

Social Networks Shape the Transmission Dynamics of Hepatitis C Virus

Hepatitis C virus (HCV) infects 170 million people worldwide, and is a major public health problem in Brazil, where over 1% of the population may be infected and where multiple viral genotypes co-circulate. Chronically infected individuals are both the source of transmission to others and are at risk for HCV-related diseases, such as liver cancer and cirrhosis. Before the adoption of anti-HCV control measures in blood banks, this virus was mainly transmitted via blood transfusion. Today, needle sharing among injecting drug users is the most common form of HCV transmission. Of particular importance is that HCV prevalence is growing in non-risk groups. Since there is no vaccine against HCV, it is important to determine the factors that control viral transmission in order to develop more efficient control measures. However, despite the health costs associated with HCV, the factors that determine the spread of virus at the epidemiological scale are often poorly understood. Here, we sequenced partial NS5b gene sequences sampled from blood samples collected from 591 patients in São Paulo state, Brazil. We show that different viral genotypes entered São Paulo at different times, grew at different rates, and are associated with different age groups and risk behaviors. In particular, subtype 1b is older and grew more slowly than subtypes 1a and 3a, and is associated with multiple age classes. In contrast, subtypes 1a and 3b are associated with younger people infected more recently, possibly with higher rates of sexual transmission. The transmission dynamics of HCV in São Paulo therefore vary by subtype and are determined by a combination of age, risk exposure and underlying social network. We conclude that social factors may play a key role in determining the rate and pattern of HCV spread, and should influence future intervention policies

The burden of dengue: Jundiaí, Brazil -January 2010

Objective: To study the antibody prevalence against dengue in the municipality of Jundiaí, São Paulo, Brazil, due to the low number of official confirmed autochthonous cases. Methods: A serological study on dengue infection was conducted during January 2010 and previous reports on dengue and entomological surveillance during that period were reviewed. Results: A prevalence of 7.8% IgG positive (68:876) was found. Furthermore, based on the detection of IgM antibodies in five samples, it was observed that the incidence of dengue in the city at the time of the survey contrasts with the absence of notifications by local health authorities over the same period of time. Conclusion: These results highlight the discrepancies between the actual and the detected number of dengue infections, possibly due to significant numbers of asymptomatic infections aggravated by difficulties with dengue clinical diagnosis. Keyword

Detection of four dengue serotypes suggests rise in hyperendemicity in urban centers of Brazil

FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo) 2010/19059-7FAPESP 2011/17071-2 and 2013/10382-8CNP