Evidence for a Novel Mechanism of Influenza Virus-Induced Type I Interferon Expression by a Defective RNA-Encoded Protein

نویسندگان

  • Yvonne Boergeling
  • Timofey S. Rozhdestvensky
  • Mirco Schmolke
  • Patricia Resa-Infante
  • Thomas Robeck
  • Gerrit Randau
  • Thorsten Wolff
  • Gülsah Gabriel
  • Jürgen Brosius
  • Stephan Ludwig
  • Carolina B. Lopez
چکیده

Influenza A virus (IAV) defective RNAs are generated as byproducts of error-prone viral RNA replication. They are commonly derived from the larger segments of the viral genome and harbor deletions of various sizes resulting in the generation of replication incompatible viral particles. Furthermore, small subgenomic RNAs are known to be strong inducers of pattern recognition receptor RIG-I-dependent type I interferon (IFN) responses. The present study identifies a novel IAV-induced defective RNA derived from the PB2 segment of A/Thailand/1(KAN-1)/2004 (H5N1). It encodes a 10 kDa protein (PB2∆) sharing the N-terminal amino acid sequence of the parental PB2 protein followed by frame shift after internal deletion. PB2∆ induces the expression of IFNβ and IFN-stimulated genes by direct interaction with the cellular adapter protein MAVS, thereby reducing viral replication of IFN-sensitive viruses such as IAV or vesicular stomatitis virus. This induction of IFN is completely independent of the defective RNA itself that usually serves as pathogen-associated pattern and thus does not require the cytoplasmic sensor RIG-I. These data suggest that not only defective RNAs, but also some defective RNA-encoded proteins can act immunostimulatory. In this particular case, the KAN-1-induced defective RNA-encoded protein PB2∆ enhances the overwhelming immune response characteristic for highly pathogenic H5N1 viruses, leading to a more severe phenotype in vivo.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Expression of Influenza Heamagglutinin Globular Head in Different Eukaryotic Cells

Background and Aims: Influenza (flu) is a respiratory infection in mammals and birds. It is caused by an RNA virus in the family Orthomyxoviridae. The virus is divided into three main types. Influenza virus type A is found in a wide variety of bird and mammal species and can undergo major shifts in immunological properties. Hemagglutinin (HA) is an important influenza virus surface antigen that...

متن کامل

Prokaryotic Expression of Influenza A virus Nucleoprotein Fused to Mycobacterial Heat Shock Protein70

Background and Aims: The novel approaches in influenza vaccination have targeted more conserved viral proteins such as nucleoprotein (NP) to provide cross protection against all serotypes of influenza A viruses. Influenza specific cytotoxic T lymphocytes (CTL) are able to lyse influenza-infected cells by recognition of NP, the major target molecule in virus for CTL responses. On the other hand,...

متن کامل

Over Expression of Influenza Virus M2 Protein in Prokaryotic System

Background and Aims: Influenza A virus of Orthomyxoviridae family is able to create pandemic influenza. Vaccination is the most effective way to prevent influenza virus infection. Matrix protein 2 (M2) is a homotetramer ion channel with 97 amino acids length and highly conserved among influenza viruses and is considered for development of a universal influenza vaccine. Materials and Methods: We...

متن کامل

Pomegranate peel extract inhibits internalization and replication of the influenza virus: An in vitro study

Objective: Influenza virus, which is associated with high level of morbidity and mortality, has been recently considered a public health concern; however, the methods of choice to control and treat it are limited. Our previous study showed anti-influenza virus activity of pomegranate peel extract (PPE). In this study, the mechanism through which PPE acts against influenza virus...

متن کامل

Immunologic Evaluation of DNA Vaccine Encoding Influenza Virus M2 Gene in Type A- Influenza Mice Model

Abstract Background and Objective: The M2 gene expressing the conserved protein in influenza virus can be used to make a single-dose vaccine with permanent immunity. Material and Methods: The mice were allocated to one case group immunized with pcDNA3-M2 and two control groups with pcDNA and PBS, in three dozes with interval of two weeks. Two weeks after the last injection, Cellular imm...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 11  شماره 

صفحات  -

تاریخ انتشار 2015