<i>In Vitro</i> Susceptibility of Adenovirus to Antiviral Drugs is Species-Dependent

TLDR

Adenovirus infections are a frequent and serious complication after allogeneic hematopoietic stem cell transplantation, and first‑line therapy with cidofovir or ribavirin has yielded variable results. The study aimed to evaluate the in‑vitro susceptibility of cidofovir and ribavirin against adenovirus reference strains from all six species and clinical isolates using HEp‑2 cells. The authors tested drug susceptibility by treating HEp‑2 cells infected with reference strains from each of the six adenovirus species and clinical isolates, measuring replication inhibition. Cidofovir inhibited replication of all tested adenovirus serotypes across species, whereas ribavirin was effective only against species C serotypes, with all other species—including clinical isolates and those tested in PLC, A549, and 293 cells—remaining resistant, indicating ribavirin would likely be ineffective for non‑C species infections post‑HSCT.

Abstract

Adenovirus infections are a frequent and serious complication following allogeneic haematopoietic stem cell transplantation (HSCT). The antiviral drugs cidofovir and ribavirin have been used as first-line therapy for disseminated infections with variable results. In the present study, in vitro susceptibility to these two drugs was evaluated on HEp-2 cells in adenovirus reference strains representing serotypes of each of the six species and in clinical isolates. Susceptibility to cidofovir was comparable between species with inhibition of replication of all tested serotypes in a narrow dose range (IC50=17-81 microM). However, susceptibility to ribavirin was highly dependent on the species. Serotypes from species A, B, D, E and F were all resistant to ribavirin (IC50=396 to >500 microM). Only replication of serotypes from species C was inhibited by ribavirin (IC50=48-108 microM). This species-dependent susceptibility of adenovirus to ribavirin was confirmed in clinical isolates. When tested on other cell lines (PLC, A549 and 293), all species were revealed to be resistant to ribavirin. If our in vitro findings are predictive of virological responses in vivo, these results suggest that ribavirin would not be effective for management of non-C species adenovirus infections after HSCT.