Identification and Structural Aspects of G-Quadruplex-Forming Sequences from the Influenza A Virus Genome.

Maria Tomaszewska,Marta Szabat,Ryszard Kierzek,Karolina Zielińska

doi:10.3390/ijms22116031

Abstract

Influenza A virus (IAV) causes seasonal epidemics and sporadic pandemics, therefore is an important research subject for scientists around the world. Despite the high variability of its genome, the structure of viral RNA (vRNA) possesses features that remain constant between strains and are biologically important for virus replication. Therefore, conserved structural motifs of vRNA can represent a novel therapeutic target. Here, we focused on the presence of G-rich sequences within the influenza A/California/07/2009(H1N1) genome and their ability to form RNA G-quadruplex structures (G4s). We identified 12 potential quadruplex-forming sequences (PQS) and determined their conservation among the IAV strains using bioinformatics tools. Then we examined the propensity of PQS to fold into G4s by various biophysical methods. Our results revealed that six PQS oligomers could form RNA G-quadruplexes. However, three of them were confirmed to adopt G4 structures by all utilized methods. Moreover, we showed that these PQS motifs are present within segments encoding polymerase complex proteins indicating their possible role in the virus biology.

Highlights

Influenza virus, due to its pandemic potential, became an interesting subject in various biological research projects
Based on the literature we know that the secondary structure of viral RNA (vRNA) is highly conserved among viral strains and biologically important for virus life cycle [7]
The viral replication, RNA packaging or its recognition by the host immune system are controlled by the RNA structure

Summary

Introduction

Due to its pandemic potential, became an interesting subject in various biological research projects. The influenza A virus (IAV) is gaining a lot of attention because of its responsibility for most of the pandemic outbreaks [1], the ability to infect fowl, humans and other mammals, and the highest zoonotic potential allowing the virus to cross the barrier from animals to humans [2] This is possible due to the reassortment (antigenic shift) of the viral RNA (vRNA) segments during the co-infection with different IAV strains [3]. Besides this ability, there are other IAV traits that make it such a serious threat to public health, i.e., easy transmission, fast adaptation to the particular host immune system, and unceasing evolutionary dynamics correlated with appearing point mutations in the viral genome (antigenic drift). It is important to discover novel therapeutic strategies and anti-influenza drugs with a new mode of action

Methods

Results

Conclusion