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

Noninvasive western lowland gorilla's health monitoring: A decade of simian immunodeficiency virus surveillance in southern Cameroon.

Simian immunodeficiency virus (SIVgor) causes persistent infection in critically endangered western lowland gorillas (Gorilla gorilla gorilla) from west central Africa. SIVgor is closely related to chimpanzee and human immunodeficiency viruses (SIVcpz and HIV-1, respectively). We established a noninvasive method that does not interfere with gorillas' natural behaviour to provide wildlife pathogen surveillance and health monitoring for conservation. A total of 1,665 geo-referenced fecal samples were collected at regular intervals from February 2006 to December 2014 (123 sampling days) in the Campo-Ma'an National Park (southwest Cameroon). Host genotyping was performed using microsatellite markers, SIVgor infection was identified by serology and genetic amplification was attempted on seropositive individuals. We identified at least 125 distinct gorillas, 50 were resampled (observed 3.5 times in average) and 38 were SIVgor+ (seven individuals were seroconverters). Six groups of gorillas were identified based on the overlapping occurrence of individuals with apparent high rates of gene flow. We obtained SIVgor genetic sequences from 25 of 38 seropositive genotyped gorillas and showed that the virus follows exponential growth dynamics under a strict molecular clock. Different groups shared SIVgor lineages demonstrating intergroup viral spread and recapture of positive individuals illustrated intra-host viral evolution. Relatedness and relationship genetic analysis of gorillas together with Bayesian phylogenetic inference of SIVgor provided evidence suggestive of vertical transmission. In conclusion, we provided insights into gorilla social dynamics and SIVgor evolution and emphasized the utility of noninvasive sampling to study wildlife health populations. These findings contribute to prospective planning for better monitoring and conservation

Dengue Virus Type 3 Adaptive Changes during Epidemics in Sao Jose de Rio Preto, Brazil, 2006–2007

Global dengue virus spread in tropical and sub-tropical regions has become a major international public health concern. It is evident that DENV genetic diversity plays a significant role in the immunopathology of the disease and that the identification of polymorphisms associated with adaptive responses is important for vaccine development. The investigation of naturally occurring genomic variants may play an important role in the comprehension of different adaptive strategies used by these mutants to evade the human immune system. In order to elucidate this role we sequenced the complete polyprotein-coding region of thirty-three DENV-3 isolates to characterize variants circulating under high endemicity in the city of Sao Jose de Rio Preto, Brazil, during the onset of the 2006-07 epidemic. By inferring the evolutionary history on a local-scale and estimating rates of synonymous (dS) and nonsynonimous (dN) substitutions, we have documented at least two different introductions of DENV-3 into the city and detected 10 polymorphic codon sites under significant positive selection (dN/dS > 1) and 8 under significant purifying selection (dN/dS < 1). We found several polymorphic amino acid coding sites in the envelope (15), NS1 (17), NS2A (11), and NS5 (24) genes, which suggests that these genes may be experiencing relatively recent adaptive changes. Furthermore, some polymorphisms correlated with changes in the immunogenicity of several epitopes. Our study highlights the existence of significant and informative DENV variability at the spatio-temporal scale of an urban outbreak

Using phylogenetics to infer HIV-1 transmission direction between known transmission pairs.

Inferring the transmission direction between linked individuals living with HIV provides unparalleled power to understand the epidemiology that determines transmission. Phylogenetic ancestral-state reconstruction approaches infer the transmission direction by identifying the individual in whom the most recent common ancestor of the virus populations originated. While these methods vary in accuracy, it is unclear why. To evaluate the performance of phylogenetic ancestral-state reconstruction to determine the transmission direction of HIV-1 infection, we inferred the transmission direction for 112 transmission pairs where transmission direction and detailed additional information were available. We then fit a statistical model to evaluate the extent to which epidemiological, sampling, genetic, and phylogenetic factors influenced the outcome of the inference. Finally, we repeated the analysis under real-life conditions with only routinely available data. We found that whether ancestral-state reconstruction correctly infers the transmission direction depends principally on the phylogeny's topology. For example, under real-life conditions, the probability of identifying the correct transmission direction increases from 32%-when a monophyletic-monophyletic or paraphyletic-polyphyletic tree topology is observed and when the tip closest to the root does not agree with the state at the root-to 93% when a paraphyletic-monophyletic topology is observed and when the tip closest to the root agrees with the root state. Our results suggest that documenting larger differences in relative intrahost diversity increases our confidence in the transmission direction inference of linked pairs for population-level studies of HIV. These findings provide a practical starting point to determine our confidence in transmission direction inference from ancestral-state reconstruction

Using machine learning and big data to explore the drug resistance landscape in HIV.

Drug resistance mutations (DRMs) appear in HIV under treatment pressure. DRMs are commonly transmitted to naive patients. The standard approach to reveal new DRMs is to test for significant frequency differences of mutations between treated and naive patients. However, we then consider each mutation individually and cannot hope to study interactions between several mutations. Here, we aim to leverage the ever-growing quantity of high-quality sequence data and machine learning methods to study such interactions (i.e. epistasis), as well as try to find new DRMs. We trained classifiers to discriminate between Reverse Transcriptase Inhibitor (RTI)-experienced and RTI-naive samples on a large HIV-1 reverse transcriptase (RT) sequence dataset from the UK (n ≈ 55, 000), using all observed mutations as binary representation features. To assess the robustness of our findings, our classifiers were evaluated on independent data sets, both from the UK and Africa. Important representation features for each classifier were then extracted as potential DRMs. To find novel DRMs, we repeated this process by removing either features or samples associated to known DRMs. When keeping all known resistance signal, we detected sufficiently prevalent known DRMs, thus validating the approach. When removing features corresponding to known DRMs, our classifiers retained some prediction accuracy, and six new mutations significantly associated with resistance were identified. These six mutations have a low genetic barrier, are correlated to known DRMs, and are spatially close to either the RT active site or the regulatory binding pocket. When removing both known DRM features and sequences containing at least one known DRM, our classifiers lose all prediction accuracy. These results likely indicate that all mutations directly conferring resistance have been found, and that our newly discovered DRMs are accessory or compensatory mutations. Moreover, apart from the accessory nature of the relationships we found, we did not find any significant signal of further, more subtle epistasis combining several mutations which individually do not seem to confer any resistance

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

Rapid Confirmation of the Zaire Ebola Virus in the Outbreak of the Equateur Province in the Democratic Republic of Congo: Implications for Public Health Interventions.

Ten days after the declaration of the Ebola outbreak in the Democratic Republic of Congo, rapid identification of the species Zaire Ebola virus using partial gene amplification and nanopore sequencing backed up the use of the recombinant vesicular stomatitis virus-Zaire Ebola virus vaccine in the recommended ring vaccination strategy

Multiplex detection of antibodies to Chikungunya, O'nyong-nyong, Zika, Dengue, West Nile and Usutu viruses in diverse non-human primate species from Cameroon and the Democratic Republic of Congo.

BACKGROUND: Epidemic arbovirus transmission occurs among humans by mosquito bites and the sylvatic transmission cycles involving non-human primates (NHPs) still exists. However, limited data are available on the extent in NHPs infections and their role. In this study, we have developed and validated a high-throughput serological screening tool to study the circulation of multiple arboviruses that represent a significant threat to human health, in NHPs in Central Africa. METHODOLOGY/PRINCIPAL FINDINGS: Recombinant proteins NS1, envelope domain-3 (DIII) for the dengue (DENV), yellow fever (YFV), usutu (USUV), west nile (WNV) and zika (ZIKV) and envelope 2 for the chikungunya (CHIKV) and o'nyong-nyong (ONNV) were coupled to Luminex beads to detect IgG directed against these viruses. Evaluation of test performance was made using 161 human sera of known arboviral status (66 negative and 95 positive). The sensitivity and specificity of each antigen were determined by statistical methods and ROC curves (except for ONNV and USUV). All NS1 antigens (except NS1-YFV), CHIKV-E2 and WNV-DIII had sensitivities and specificities > 95%. For the other DIII antigens, the sensitivity was low, limiting the interest of their use for seroprevalence studies. Few simultaneous reactions were observed between the CHIKV+ samples and the NS1 antigens to the non-CHIKV arboviruses. On the other hand, the DENV+ samples crossed-reacted with NS1 of all the DENV serotypes (1 to 4), as well as with ZIKV, USUV and to a lesser extent with YFV. A total of 3,518 samples of 29 species of NHPs from Cameroon and the Democratic Republic of Congo (DRC) were tested against NS1 (except YFV), E2 (CHIKV/ONNV) and DIII (WNV) antigens. In monkeys (n = 2,100), the global prevalence varied between 2 and 5% for the ten antigens tested. When we stratified by monkey's biotope, the arboreal species showed the highest reactivity. In monkeys from Cameroon, the highest IgG prevalence were observed against ONNV-E2 and DENV2-NS1 with 3.95% and 3.40% respectively and in DRC, ONNV-E2 (6.63%) and WNV-NS1 (4.42%). Overall prevalence was low in apes (n = 1,418): ranging from 0% for USUV-NS1 to 2.6% for CHIKV-E2. However, a very large disparity was observed among collection site and ape species, e.g. 18% (9/40) and 8.2% (4/49) of gorillas were reactive with CHIKV-E2 or WNV-NS1, respectively in two different sites in Cameroon. CONCLUSIONS/SIGNIFICANCE: We have developed a serological assay based on Luminex technology, with high specificity and sensitivity for simultaneous detection of antibodies to 10 antigens from 6 different arboviruses. This is the first study that evaluated on a large scale the presence of antibodies to arboviruses in NHPs to evaluate their role in sylvatic cycles. The overall low prevalence (<5%) in more than 3,500 NHPs samples from Cameroon and the DRC does not allow us to affirm that NHP are reservoirs, but rather, intermediate hosts of these viruses