Bortezomib inhibits infectious DENV production in primary monocytes.

<p>Infectious DENV in cell culture supernatant was measured using plaque assay, and the percent inhibition of infectious DENV production after bortezomib treatment compared to DMSO treatment was calculated. At doses of bortezomib that is minimally toxic to primary monocytes, a significant dose-dependent decrease in virus titers was observed for different strains of all 4 dengue serotypes, (A) DENV1, (B) DENV2, (C) DENV3 and (D) DENV4, after drug treatment in primary monocytes. The identity of the clinical isolate is indicated next to a distinct colored dot. The bortezomib concentration that inhibited 50% of virus replication (in parentheses) was less than 20 nM for DENV1, 2, 3 and 4, respectively. (E) Bortezomib also inhibited 50% of virus production of the attenuated strain of yellow fever virus, YF17D, at a concentration of 0.5 nM. (F) Epoxomicin, another proteasome inhibitor, was able to reduce DENV titers by plaque assay in a dose-dependent manner for all 4 dengue serotypes. Mean ± SD. N = 4.