Antiviral therapeutic approaches for human rhinovirus infections

Casanova, Victor; Sousa, Filipa H; Stevens, Craig; Barlow, Peter G

When a complex and physiological model of fully differentiated HPBEC in an air-liquid interface was used to address the effects of calcitriol on RV16 replication, no reduction in viral load was observed [96] . However, clear effects on cell morphology and replication were noted. While the doses of calcitriol used in this study were lower (10 nM) than above mentioned studies, these differences underscore the importance of the cell and delivery system used to study vitamin D effects. In this regard, daily delivery of 2 μg of calcitriol in tablet form for 1 week failed to significantly increase nasal LL-37 concentrations in a double-blind, placebo-controlled study involving healthy or asthmatic subjects [97] . Interestingly, the same group reported that exposing fully differentiated HPBEC to proinflammatory cytokines such as TNF-α and IL-1β, prior to vitamin D treatment, lessened the induction of LL-37. This reduced the overall antimicrobial effects of vitamin D due to an alteration in the metabolic pathway [98] . These observations indicate that further work in this area is required, particularly in the context of chronic inflammatory lung diseases, as this finding could limit the benefits of vitamin D supplementation strategies.