Abstract

Influenza A virus is a successful parasite and requires host factors to complete its life cycle. Prop5 is an antisense oligonucleotide, targeting programmed cell death protein 5 (PDCD5). In this study, we tested the antiviral activity of prop5 against mouse-adapted A/FM/1/47 strain of influenza A virus in a mouse model. Prop5 intranasally administered the mice at dosages of 10 and 20 mg/kg/d at 24 h and 30 min before infection, provided 80% and 100% survival rates and prolonged mean survival days in comparison with influenza virus-infected mice (both p < 0.01). Moreover, viral titres in mice pretreated with prop5, at dose of 10 and 20 mg/kg/d, had declined significantly on day two, four, and six post-infection compared with the yields in infected mice (p < 0.05 or p < 0.01); lung index in mice pretreated with prop5 (20 mg/kg/d) had been inhibited on day six post-infection (p < 0.05). Western blotting and immunohistochemistry showed that prop5 could down-regulate the PDCD5 protein expression levels in lung tissues of infected mice. These data indicate that antisense oligonucleotide prop5 is a promising drug for prophylaxis and control influenza virus infections and provides an insight into the host-pathogen interaction.

Highlights

  • Influenza A virus (IAV) is an RNA virus of the family Orthomyxoviridae and causes contagious respiratory disease with potentially fatal threats in both animals and humans

  • Our results suggested that prop5 could down-regulate PDCD5 expression, while exhibiting a prophylactic effect on the mouse-adapted variant of influenza virus infected mice model

  • The results showed that prop5 (20 mg/kg/d) could completely protect mice from lethal challenge with the mouse-adapted variant of influenza virus

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Summary

Introduction

Influenza A virus (IAV) is an RNA virus of the family Orthomyxoviridae and causes contagious respiratory disease with potentially fatal threats in both animals and humans. Pharmacological targeting host factors, required for influenza virus propagation, proved an alternative therapeutic strategy to minimize the likelihood of the emergence of viral resistance [8]. Human host cellular factors involved in IAV replication, respectively. They further confirmed that inhibition of vATPase, CAMK2B, CLK1, and Cdkn1b blocked influenza virus replication [8,9]. Two-dimensional electrophoresis and Western blotting demonstrated that levels of PDCD5 expression are up-regulated in human lung adenocarcinoma epithelial cells (A549) after IAV infection [11]. MRNA, has been validated to down-regulate PDCD5 expression in A549 cells and inhibit propagation of influenza A/jingfang/1/86 (H1N1) virus. Our results suggested that prop could down-regulate PDCD5 expression, while exhibiting a prophylactic effect on the mouse-adapted variant of influenza virus infected mice model

Prop5 Protected Animals from Influenza Virus Infections
Prop5 Decreased the Lung Infection Parameters
Experimental Section
Antiviral Activity of prop5 in Vivo
Lung Infection Parameters
Conclusions
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