Dataset Information

Phylogenesys and homology modeling in Zika virus epidemic: food for thought.

ABSTRACT: Zika virus (ZIKV) is an emerging Flavivirus that have recently caused an outbreak in Brazil and rapid spread in several countries. In this study, the consequences of ZIKV evolution on protein recognition by the host immune system have been analyzed. Evolutionary analysis was combined with homology modeling and T-B cells epitope predictions. Two separate clades, the African one with the Uganda sequence, as the most probable ancestor, and the second one containing all the most recent sequences from the equatorial belt were identified. Brazilian strains clustered all together and closely related to the French Polynesia isolates. A strong presence of a negatively selected site in the envelope gene (Env) protein was evidenced, suggesting a probable purging of deleterious polymorphisms in functionally important genes. Our results show relative conservancy of ZIKV sequences when envelope and other non-structural proteins (NS3 and NS5) are analyzed by homology modeling. However, some regions within the consensus sequence of NS5 protein and to a lesser extent in the envelope protein, show localized high mutation frequency corresponding to a considerable alteration in protein stability. In terms of viral immune escape, envelope protein is under a higher selective pressure than NS5 and NS3 proteins for HLA class I and II molecules. Moreover, envelope mutations that are not strictly related to T-cell immune responses are mostly located on the surface of the protein in putative B-cell epitopes, suggesting an important contribution of B cells in the immune response as well.

SUBMITTER: Angeletti S

PROVIDER: S-EPMC5189860 | biostudies-literature | 2016 Oct - Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Phylogenesys and homology modeling in Zika virus epidemic: food for thought.

Angeletti Silvia S Lo Presti Alessandra A Giovanetti Marta M Grifoni Alba A Amicosante Massimo M Ciotti Marco M Alcantara Luiz-Carlos J LJ Cella Eleonora E Ciccozzi Massimo M

Pathogens and global health 20160927 7-8

Zika virus (ZIKV) is an emerging Flavivirus that have recently caused an outbreak in Brazil and rapid spread in several countries. In this study, the consequences of ZIKV evolution on protein recognition by the host immune system have been analyzed. Evolutionary analysis was combined with homology modeling and T-B cells epitope predictions. Two separate clades, the African one with the Uganda sequence, as the most probable ancestor, and the second one containing all the most recent sequences fro ...[more]

PMID: 27670692

Similar Datasets

Project description:Originating from African forests, Zika virus (ZIKV) has now emerged worldwide in urbanized areas, mainly transmitted by Aedes aegypti mosquitoes. Although Aedes albopictus can transmit ZIKV experimentally and was suspected to be a ZIKV vector in Central Africa, the potential of this species to sustain virus transmission was yet to be uncovered until the end of 2019, when several autochthonous transmissions of the virus vectored by Ae. albopictus occurred in France. Aside from these few locally acquired ZIKV infections, most territories colonized by Ae. albopictus have been spared so far. The risk level of ZIKV emergence in these areas remains however an open question. To assess Ae. albopictus' vector potential for ZIKV and identify key virus outbreak predictors, we built a complete framework using the complementary combination of (i) dose-dependent experimental Ae. albopictus exposure to ZIKV followed by time-dependent assessment of infection and systemic infection rates, (ii) modeling of intra-human ZIKV viremia dynamics, and (iii) in silico epidemiological simulations using an Agent-Based Model. The highest risk of transmission occurred during the pre-symptomatic stage of the disease, at the peak of viremia. At this dose, mosquito infection probability was estimated to be 20%, and 21 days were required to reach the median systemic infection rates. Mosquito population origin, either temperate or tropical, had no impact on infection rates or intra-host virus dynamic. Despite these unfavorable characteristics for transmission, Ae. albopictus was still able to trigger and yield large outbreaks in a simulated environment in the presence of sufficiently high mosquito biting rates. Our results reveal a low but existing epidemic potential of Ae. albopictus for ZIKV, that might explain the absence of large scale ZIKV epidemics so far in territories occupied only by Ae. albopictus. They nevertheless support active surveillance and eradication programs in these territories to maintain the risk of emergence to a low level.

Project description:Each new virus introduced into the human population could potentially spread and cause a worldwide epidemic. Thus, early quantification of epidemic spread is crucial. Real-time sequencing followed by Bayesian phylodynamic analysis has proven to be extremely informative in this respect. Bayesian phylodynamic analyses require a model to be chosen and prior distributions on model parameters to be specified. We study here how choices regarding the tree prior influence quantification of epidemic spread in an emerging epidemic by focusing on estimates of the parameters clock rate, tree height, and reproductive number in the currently ongoing Zika virus epidemic in the Americas. While parameter estimates are quite robust to reasonable variations in the model settings when studying the complete data set, it is impossible to obtain unequivocal estimates when reducing the data to local Zika epidemics in Brazil and Florida, USA. Beyond the empirical insights, this study highlights the conceptual differences between the so-called birth-death and coalescent tree priors: while sequence sampling times alone can strongly inform the tree height and reproductive number under a birth-death model, the coalescent tree height prior is typically only slightly influenced by this information. Such conceptual differences together with non-trivial interactions of different priors complicate proper interpretation of empirical results. Overall, our findings indicate that phylodynamic analyses of early viral spread data must be carried out with care as data sets may not necessarily be informative enough yet to provide estimates robust to prior settings. It is necessary to do a robustness check of these data sets by scanning several models and prior distributions. Only if the posterior distributions are robust to reasonable changes of the prior distribution, the parameter estimates can be trusted. Such robustness tests will help making real-time phylodynamic analyses of spreading epidemic more reliable in the future.

Dataset Information

Phylogenesys and homology modeling in Zika virus epidemic: food for thought.

Publications

Phylogenesys and homology modeling in Zika virus epidemic: food for thought.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets