Endogenous Expression of an RNA-Hydrolyzing Minibody Enhances the Therapeutic Effects Against Influenza a Virus Compared to Therapeutically Intranasal Administration

Abstract

Influenza pandemics have had devastating impacts in the 20th and 21st centuries, resulting in millions of deaths. It is challenging to control the influenza virus through antiviral drugs due to its rapid evolution to evade the host immune system. The 3D8 single chain variable fragment (scFv) protein, known for its nuclease activity against DNA and RNA viruses, has demonstrated broad antiviral properties in various models. In this study, we investigated the impact of administration routes and dosages on the distribution of exogenously administered 3D8 scFv. Our results suggested that repeated intranasal (IN) injection primarily targets lung tissue, while intravenous (IV) administration ensures systemic distribution, including lung tissues via the bloodstream. Furthermore, we explored the efficacy of exogenous and endogenous 3D8 scFv in inhibiting influenza A virus (H1N1/PR8) replication in mouse models. Our findings revealed that while both approaches exhibited antiviral activity, with constitutive pre-infection expression of 3D8 scFv showed 100% survival, whereas mice receiving exogenous 3D8 scFv post-infection exhibited 33.3% survival. These findings highlight the potential of 3D8 scFv as a promising antiviral strategy against influenza and suggest its possible applications in transgenic livestock for future disease control.