A Coupled Mathematical Model of the Intracellular Replication of Dengue Virus and the Host Cell Immune Response to Infection.

Dengue virus (DV) is a positive-strand viral RNA of the genus flavivirus. It is one of the most prevalent virus mosquitoes, infects 390 million people globally per year. DV infection clinical spectrum ranges from asymptomatic course of severe complications such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), the latter due to a severe plasma leakage. 

Given that the outcome of an infection may be determined by the kinetics of viral replication and antiviral host cell immune response (HIR) it is very important to understand the interaction between the two parameters. In this study, we used a mathematical model to characterize and understand the complex interactions between DV intracellular replication and host cell's defense mechanisms. We first measured the viral RNA, viral proteins, and the production of virus particles in Huh7 cells, which indicates the intrinsic antiviral responses are notoriously weak. Based on these measurements, we developed a detailed intracellular replication model DV. 

We then measured the IFN replication competent A549 cells and use this data to multiple replication model with a model that describes the activation of IFN and IFN production is stimulated genes (ISGs), as well as their interaction with DV replication. By comparing the specific replication DV cell lines, we found that the host factors involved in the formation and replication of the virus particle production complex is essential for the replication efficiency. 

Regarding the possibility of mode of action of HIR, fits our model indicates that HIR which mainly affects RNA translation initiation DV, DV cytosolic degradation of RNA, and infection of naive cells. We further analyzed the potential of direct-acting antiviral drugs targeting different processes of the life cycle of DV in silico and found that targeting viral RNA Tubes synthesis and assembly and the release of the most promising drug targets anti-DV.

Execution protein actin, profilin, regulate intracellular vesicle transport in Leishmania.

Profilins is a key regulator of actin dynamics in all eukaryotic cells. However, little information is available about their biochemical properties and functions in kinetoplastids, such as Trypanosoma and Leishmania. We show here that the Leishmania parasite revealed that only one homolog of profilin (LdPfn), which catalyses nucleotide exchange at the G-actin and promote actin polymerization at low concentrations. However, at high concentrations, it strongly inhibits actin polymerization process with the absorption of the monomer. immune 

We further demonstrate that LdPfn bind to actin in Leishmania promastigotes, either by immunofluorescence microscopy and IgG affinity chromatography. Furthermore, we revealed that this protein binding motifs in addition to poly-L-proline, it is also more efficient binding to PI (3,5) P2, which was found in early or late endosomes or lysosomes, instead of PI (4,5) P2 and PI ( 3,4,5) P3.

 In addition, we showed that profilin screen heterozygous mutant growth is significantly slower and activity of intracellular vesicle trafficking, overturned in episomal gene complementation. Together, these findings suggest that profilin Regulates intracellular vesicle trafficking Leishmania may be through binding polyphosphoinositides.