CCCH-type zinc-finger antiviral protein (ZAP) is a host factor that restricts the infection of many viruses mainly through RNA degradation, translation inhibition and innate immune responses. So far, only one flavivirus, yellow fever virus, has been reported to be ZAP-resistant. Here, we investigated the antiviral potential of human ZAP (isoform ZAP-L and ZAP-S) against three flaviviruses, Japanese encephalitis virus (JEV), dengue virus (DENV) and Zika virus (ZIKV). Infection of JEV but not DENV or ZIKV was blocked by ZAP overexpression, and depletion of endogenous ZAP enhanced JEV replication. ZAP hampered JEV translation and targeted viral RNA for 3′-5′ RNA exosome-mediated degradation. The zinc-finger motifs of ZAP were essential for RNA targeting and anti-JEV activity. JEV 3′-UTR, especially in the region with dumbbell structures and high content of CG dinucleotide, was mapped to bind ZAP and confer sensitivity to ZAP. In summary, we identified JEV as the first ZAP-sensitive flavivirus. ZAP may act as an intrinsic antiviral factor through specific RNA binding to fight against JEV infection.

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The diffusiophoresis of a charged sphere along the axis of a circular microtube filled with an electrolyte solution is studied theoretically. The tube wall may be either nonconductive and impermeable or prescribed with a linear electrolyte concentration distribution. The electric double layers at the solid surfaces are thin, but the diffuse-layer polarization effect over the particle surface is considered. The general solutions to the electrokinetic differential equations are expressed in spherical and cylindrical coordinates, whereas the boundary conditions at the particle surface are satisfied by a collocation technique. The collocation solutions for the diffusiophoretic velocity of the particle, which are in good agreement with the asymptotic formula derived from a reflection method, are obtained for various values of the radius ratio and zeta potential ratio between the particle and the microtube and of other relevant parameters. The contributions from the diffusioosmotic flow along the tube wall and wall-corrected diffusiophoretic driving force to the particle velocity can be superimposed due to the linearity. Although the diffusiophoretic velocity in an uncharged microtube is in general a decreasing function of the particle-to-tube radius ratio and can reverse its direction, it can increase with increases in this ratio due to the competition of the wall effects of possible electrochemical enhancement and hydrodynamic retardation to the particle motion. When the zeta potentials associated with the tube and particle are equivalent, the diffusioosmotic flow induced by the tube wall dominates the diffusiophoretic motion.

SARS-CoV-2 breakthrough infection occurs due to waning immunity time-to-vaccine, to which the globally-dominant, highly-contagious Delta variant is behind the scene. In the primary 2-dose and booster series of clinical Phase-1 trial, UB-612 vaccine, which contains S1-RBD and synthetic Th/CTL peptide pool for activation of humoral and T-cell immunity, induces substantial, prolonged viral-neutralizing antibodies that goes parallel with a long-lasting T-cell immunity; and a booster (3rd ) dose can prompt recall of memory immunity to induce profound, striking antibodies with the highest level of 50% viral-neutralizing GMT titers against live Delta variant reported for any vaccine. The unique design of S1-RBD only plus multitope T-cell peptides may have underpinned UB-612’s potent anti-Delta effect, while the other full S protein-based vaccines are affected additionally by mutations in the N-terminal domain sequence which contains additional neutralizing epitopes. UB-612, safe and well-tolerated, could be effective for boosting other vaccine platforms that have shown modest homologous boosting. [Funded by United Biomedical Inc., Asia; ClinicalTrials.gov ID: NCT04967742 and NCT04545749]