Growth of Zika virus in human reconstituted respiratory, intestinal, vaginal and neural tissues.

OBJECTIVES: Zika virus (ZIKV) is mostly mosquito borne but it can also be transmitted via the sexual route and persists in semen for a prolonged time. Moreover, viral RNA has been detected in breast milk, saliva, lacrimal fluids and urine, suggesting other possible transmission routes. The aim of our research is to better define ZIKV tropism. METHODS: We investigated the tropism of Asian and African strains of ZIKV using human-derived neural, vaginal, intestinal and respiratory tissues. RESULTS: Asian and African strains of ZIKV were able to grow in all tissues tested, although with different efficiency (7.3 log RNA copies released apically in vaginal tissues versus 9.8 log RNA copies released in intestinal tissues), without the need for major adaptation. CONCLUSIONS: Our results underline that ZIKV tropism may be broader than expected in humans and stress the need to better explore all possible virus-shedding sites and transmission routes.

Preparation, characterization and in vitro antiviral activity evaluation of foscarnet-chitosan nanoparticles.

A new nanoparticulate system for foscarnet delivery was prepared and evaluated. Nanoparticles were obtained by ionotropic gelation of chitosan induced by foscarnet itself, acting as an ionotropic agent in a manner similar to tripolyphosphate anion. A Doehlert design allowed finding the suitable experimental conditions. Nanoparticles were between 200 and 300nm in diameter (around 450nm after redispersion). Nanoparticle size increased after 5h, but no size increase was observed after 48h when nanoparticles were crosslinked with glutaraldehyde. Zeta potential values of noncrosslinked and crosslinked nanoparticles were between 20 and 25mV, while drug loading of noncrosslinked nanoparticles was about 40% w/w (55% w/w for crosslinked nanoparticles). Nanoparticle yield was around 25% w/w. Crosslinked nanoparticles showed a controlled drug release. Foscarnet released from nanoparticles maintained the antiviral activity of the free drug when tested in vitro against lung fibroblasts (HELF) cells infected with HCMV strain AD-169. Moreover, nanoparticles showed no toxicity on non-infected HELF cells. These nanoparticles may represent a delivery system that could improve the therapeutic effect of foscarnet.