Decoding the role of RNA sequences and their interactions in influenza A virus infection and adaptation

Abstract Influenza viruses (types A, B, C, and D) belong to the family orthomyxoviridae. Out of all the influenza types, influenza A virus (IAV) causes human pandemic outbreaks. Its pandemic potential is predominantly attributed to the genetic reassortment favored by a broad spectrum of host species that could lead to an antigenic shift along with a high rate of mutations in its genome, presenting a possibility of subtypes with heightened pathogenesis and virulence in humans (antigenic drift). In addition to antigenic shift and drift, there are several other inherent properties of its viral RNA species (vRNA, vmRNA, and cRNA) that significantly contribute to the success of specific stages of viral infection. In this review, we compile the key features of IAV RNA, such as sequence motifs and secondary structures, their functional significance in the infection cycle, and their overall impact on the virus's adaptive and evolutionary fitness. Because many of these motifs and folds are conserved, we also assess the existing antiviral approaches focused on targeting IAV RNA. This article is categorized under: RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications RNA in Disease and Development > RNA in Disease