Preventive Activity against Influenza (H1N1) Virus by Intranasally Delivered RNA-Hydrolyzing Antibody in Respiratory Epithelial Cells of Mice.

Seungchan Cho,Mun-Ju Cho,Chang-Seon Song,Sukchan Lee,Eui-Joon Kil,Sung-June Byun,Ha-Na Youn,Sungrae Cho,Kee-Eun Kim,Juhyun Hong,Gunsup Lee,Phuong Hoang

doi:10.3390/v7092863

Abstract

The antiviral effect of a catalytic RNA-hydrolyzing antibody, 3D8 scFv, for intranasal administration against avian influenza virus (H1N1) was described. The recombinant 3D8 scFv protein prevented BALB/c mice against H1N1 influenza virus infection by degradation of the viral RNA genome through its intrinsic RNA-hydrolyzing activity. Intranasal administration of 3D8 scFv (50 μg/day) for five days prior to infection demonstrated an antiviral activity (70% survival) against H1N1 infection. The antiviral ability of 3D8 scFv to penetrate into epithelial cells from bronchial cavity via the respiratory mucosal layer was confirmed by immunohistochemistry, qRT-PCR, and histopathological examination. The antiviral activity of 3D8 scFv against H1N1 virus infection was not due to host immune cytokines or chemokines, but rather to direct antiviral RNA-hydrolyzing activity of 3D8 scFv against the viral RNA genome. Taken together, our results suggest that the RNase activity of 3D8 scFv, coupled with its ability to penetrate epithelial cells through the respiratory mucosal layer, directly prevents H1N1 virus infection in a mouse model system.

Highlights

Influenza virus, a RNA virus in the family Orthomyxoviridae is an acute respiratory infectious agent that causes significant morbidity and mortality in annual epidemics and global pandemic outbreaks [1]
Based on research showing that 3D8 scFv could catalyze the viral genome and its transcripts [12], we tested the antiviral activity of endotoxin-free 3D8 scFv by treatment of purified 3D8 scFv proteins to MDCK cells
At 24 h post-infection, a less cytopathic effect (CPE) was observed under the microscope in the cells treated with 3D8 scFv compared with those treated with PBS (Figure 1A)

Summary

Introduction

A RNA virus in the family Orthomyxoviridae is an acute respiratory infectious agent that causes significant morbidity and mortality in annual epidemics and global pandemic outbreaks [1]. In 2009, the pandemic H1N1 influenza A emerged from Mexico and the United States [2,3]. During the initial phases of the 2009 H1N1 pandemic, the use of neuraminidase inhibitors for the prevention of influenza virus infection was effective when vaccines were not available [4]. Seasonal and 2009 pandemic H1N1 influenza viruses that are resistant to these drugs have emerged and subsequently spread worldwide [5,6]. Increased influenza activity was reported in North America and Europe and in several countries in. Many mutant influenza viruses such as A(H1N1)pdm and A(H3N2) have been identified, posing a great threat to worldwide public health [7,8]. There is an urgent need for the development of novel antiviral therapeutics against new influenza viruses or their mutants

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