Abstract

The influenza A virus is a human pathogen causing respiratory infections. The ability of this virus to trigger seasonal epidemics and sporadic pandemics is a result of its high genetic variability, leading to the ineffectiveness of vaccinations and current therapies. The source of this variability is the accumulation of mutations in viral genes and reassortment enabled by its segmented genome. The latter process can induce major changes and the production of new strains with pandemic potential. However, not all genetic combinations are tolerated and lead to the assembly of complete infectious virions. Reports have shown that viral RNA segments co-segregate in particular circumstances. This tendency is a consequence of the complex and selective genome packaging process, which takes place in the final stages of the viral replication cycle. It has been shown that genome packaging is governed by RNA–RNA interactions. Intersegment contacts create a network, characterized by the presence of common and strain-specific interaction sites. Recent studies have revealed certain RNA regions, and conserved secondary structure motifs within them, which may play functional roles in virion assembly. Growing knowledge on RNA structure and interactions facilitates our understanding of the appearance of new genome variants, and may allow for the prediction of potential reassortment outcomes and the emergence of new strains in the future.

Highlights

  • Influenza A virus (IAV) is responsible for common respiratory infection in human, spreading as seasonal epidemics and sporadic pandemics

  • The results showed that specific residues play significant roles in virion are organized in ribonucleoprotein complexes (vRNPs) arrangement, ensuring efficient genome packaging

  • A subset of these have been confirmed and studied by independent researchers (Table 1). Their functional role in genome packaging has been proved through mutational studies, in which structure-disturbing mutations caused the inhibition of viral replication, segment stoichiometry changes, and defective particle production

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Summary

Introduction

Influenza A virus (IAV) is responsible for common respiratory infection in human, spreading as seasonal epidemics and sporadic pandemics. A major evolutionary advantage to the virus provided by genome segmentation is that it allows for genetic reassortment that is, the exchange of segments—when at least two viruses co-infect the same cell This process is a source of genetic variability leading to the production of new viral strains with pandemic potential. From two proposed models for the incorporation of eight vRNAs into infectious IAV particles, the existence of a segment-specific packaging has been repeatedly confirmed by independent researchers [12]. This process is mediated by the interaction of RNA regions called packaging signals. The growing knowledge in this field may allow for the prediction of new strains appearing, in order to prevent infection and virus transmission in the future

RNA Structure
NP—RNA Association
RNA Interactions
Implications for the Emergence of New Strains
Influenza
Co-Segregation
Other Examples of Gene Co-Selection
Seasonal H3N2 Reassortment Potential
Role of the NP In Virion Production
Findings
Conclusions
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