Part of the book: Epidemiology
Dengue virus (DENV) is one of the most prevalent human pathogens worldwide. It causes a huge socioeconomic burden with approximately 400 million infections per year, but yet there is no vaccine or antiviral that is currently effective against the disease. DENV is spread by the mosquitoes Aedes aegypti and Aedes albopictus, and viral replication within the mosquito vector is required for transmission to human host. During its replication cycle, the virus cause significant changes to the host transcriptome profile, especially in the metabolic and trafficking pathways. Recent studies have shown a strong association between autophagy and lipid metabolism modulation.
Part of the book: Cell Biology
The study of viral infections using live cell imaging (LCI) is an important area with multiple opportunities for new developments in computational cell biology. Here, this point is illustrated by the analysis of the sub-cellular distribution of mitochondrium in cell cultures infected by Dengue virus (DENV) and in uninfected cell cultures (Mock-infections). Several videos were recorded from the overnight experiments performed in a confocal microscopy of spinning disk. The density distribution of mitochondrium around the nuclei as a function of time and space ρ(r, θ, t) was numerically modeled as a smooth interpolation function from the image data and used in further analysis. A graphical study shows that the behavior of the mitochondrial density is substantially different when the infection is present. The DENV-infected cells show a more diffuse distribution and a stronger angular variation on it. This behavior can be quantified by using some usual image processing descriptors called entropy and uniformity. Interestingly, the marked difference found in the mitochondria density distribution for mock and for infected cell is present in every frame and not an evidence of time dependence was found, which indicate that from the start of the infections the cells are showing an altered subcellular pattern in mitochondrium distribution. Ulteriorly, it would be important to study by analysis of time series for clearing if there is some tendency or approximate cycles. Those findings are suggesting that using the image descriptors entropy and uniformity it is possible to create a machine learning classifier that could recognize if a single selected cell in a culture has been infected or not.
Part of the book: Cell Biology
The cell biology of viral infections is the focus of this research, in which the role of the cytoskeleton in dengue virus (DENV) replication in cell cultures was evaluated by means of Nocodazole and Cytochalasin D treatments before and after of DENV infection. The potential contribution of cytoskeleton elements with/without the treatment of depolymerizing agents was evidenced and quantified by the subcellular distribution of viral proteins, virions produced, and viral protein quantification. The cytoskeleton is involved in DENV replication because treatments with actin microfilaments and microtubule depolymerizing agents in non-cytotoxic concentrations, affected DENV2 replication in Vero cells and decreased both the viral protein expression and infectious virion production, when compared with non-treated cells. The actin and microtubules are partly involved in DENV2 replication, since the treatment does not completely blocked viral replication, suggesting that these components are necessary but not sufficient alone for DENV2 replication in Vero cells. The structural and functional role of actin and the microtubules in replication are postulated here, opening new perspectives for understanding the architecture of the replicative complex and viral morphogenesis processes, due to the role of the cytoskeleton in the organization, recruitment, and function of the cellular elements necessary for the assembly of viral factories.
Part of the book: Cell Biology