Gripp‐Heel and the Antiviral Host‐Cell Responses against Adenovirus

Adenoviruses cause respiratory and ocular infections as well as pneumonia outbreaks in military recruits. The adenoviral infection is known to trigger a vigorous host innate response with the induction of acute inflammation, possibly playing a role in antiviral defense, but also contributes to the pathogenesis and clinical severity of invasive adenoviral infections. The cellular innate response signaling cascades and inflammatory cytokines production is induced early upon viral entry, by activation of innate danger‐sensing cellular receptors, including Toll‐like receptors (TLRs), Nod‐like receptors, and RIG‐like receptors (RLRs). Although the signals for the proinflammatory effector molecule production remain mostly unknown, one of the key components of the innate immune response are shown to be induced by adenovirus is the NLRP3 inflammasome. To date, cidofovir is the only antiviral drug employed for the treatment of severe adenovirus infection; however its use is limited by toxicity, low oral bioavailability, and variable efficacy. In this study we evaluated the in vitro antiviral activity of Gripp‐Heel against adenovirus, and further analyzed the effect of Gripp‐Heel on cellular gene transcription in an attempt to address its mechanism of action and impact on the host response. The views, opinions, and/or findings contained in this report are those of the authors and should not be construed as official Department of the Army position, policy, or decision, unless designated by other official documentation