# Longitudinal Monitoring of the Effects of Anti-Adenoviral Treatment Regimens in a Permissive In Vivo Model

## TL;DR

This study uses a hamster model to test how short-term antiviral treatments can manage adenovirus infections without causing excessive side effects.

## Contribution

The study introduces a longitudinal in vivo model for evaluating anti-adenoviral treatment regimens using luciferase-based virus monitoring.

## Key findings

- Luciferase expression allowed repeated in vivo monitoring of adenovirus replication in the same animal.
- Short-term antiviral treatment at peak replication prevented virus-associated pathology in hamsters.
- NPP-669 and valganciclovir showed high and moderate anti-adenoviral efficacy, respectively.

## Abstract

Adenovirus infections of immunocompromised patients can cause life-threatening disseminated disease. While there are presently no drugs specifically approved to treat these infections, there are several compounds that showed efficacy against adenovirus in preclinical studies. For any such compound, low toxicity is an essential requirement. As cumulative drug effects can accentuate pathology, especially in patients with other morbidities, it is important to limit antiviral exposure to what is absolutely necessary. This is achievable by monitoring the virus burden of the patients and administering antivirals to suppress virus replication to a non-pathogenic level. We modeled such a system using Syrian hamsters infected with a replication-competent adenovirus vector, in which luciferase expression is coupled to virus replication. We found that virus replication could be followed in vivo in the same animal by repeated measurement of luciferase expression. To test the utility of an interrupted treatment regimen, we used NPP-669 and valganciclovir, two antiviral compounds with high and moderate anti-adenoviral efficacy, respectively. We found that short-term treatment of adenovirus-infected hamsters at times of peak virus replication can prevent virus-associated pathology. Thus, we believe that this animal model can be used to model different treatment regimens for anti-adenoviral compounds.