Role of microparticles in dengue virus infection and its impact on medical intervention strategies

Abstract

Dengue virus (DV) is one of the most important vector-borne diseases in the world. It causes a disease that manifests as a spectrum of clinical symptoms, including dengue hemorrhagic fever. DV is proficient at diverting the immune system to facilitate transmission through its vector host, Aedes spp. mosquito. Similar to other vector-borne parasites, dengue may also require a second structural form, a virus of alternative morphology (VAM), to complete its life cycle. DV can replicate to high copy numbers in patient plasma, but no classical viral particles can be detected by ultra-structural microscopy analysis. A VAM appearing as a microparticle has been recapitulated with in vitro cell lines Meg01 and K562, close relatives to the cells harboring dengue virus in vivo. VAMs are likely to contribute to the high viremia levels observed in dengue patients. This review discusses the possible existence of a VAM in the DV life cycle.

Keywords: Aedes mosquitoes; Dengue virus; alternative virion; microparticles; vaccine; vector-borne transmission.

Figure 1

Transmission EM images of DV2-infected Vero cells and dengue patient platelets. Vero cells were infected with a multiplicity of infection equal to 5 for 18 hours, and samples were prepared as previously described [58]. Human platelets were isolated from acute dengue patients via Optiprep, and platelets were fixed with 4 percent glutaraldehyde in PBS. Samples were washed and fixed with 2 percent osmium tetraoxide and stained with uranyl acetate. Stained specimens were infiltrated with propylene oxide and epoxy resin, embedded in a polypropylene capsule and visualized with a Hitachi Transmission Electron Microscope. A) Dengue classical virions can be seen in endocytic vesicles of infected Vero cells. B and C) Dengue viral particles inside platelet vesicles isolated from two acute dengue patients. Red arrows indicate viral- particles inside virus-induced vesicle structure.

Figure 2

Transmission EM of plasma concentrate pooled from multiple patients. Plasma was spun with an ultrahigh speed at130,000xg for 30 minutes, and the pellets were prepared as described in Figure 1. Small vesicles containing virus particles were observed.