Packaging signal of influenza A virus

Abstract

Influenza A virus (IAV) contains a genome with eight single-stranded, negative-sense RNA segments that encode 17 proteins. During its assembly, all eight separate viral RNA (vRNA) segments are incorporated into virions in a selective manner. Evidence suggested that the highly selective genome packaging mechanism relies on RNA-RNA or protein-RNA interactions. The specific structures of each vRNA that contribute to mediating the packaging of the vRNA into virions have been described and identified as packaging signals. Abundant research indicated that sequences required for genome incorporation are not series and are varied among virus genotypes. The packaging signals play important roles in determining the virus replication, genome incorporation and genetic reassortment of influenza A virus. In this review, we discuss recent studies on influenza A virus packaging signals to provide an overview of their characteristics and functions.

Keywords: Incorporation; Influenza A virus; Packaging signals; RNA-RNA interaction; Reassortment.

Fig. 1

A model for selective incorporation of IAV genome. Different vRNAs are shown as lines of varied colors (red, green, yellow, blue, black, purple, cyan, and brown), and homologous gene segments from different viruses are shown as different shapes. Nucleotides with low-NP-binding may form secondary structures which are necessary for the incorporation of vRNP. The favored hypothesis of the highly selective genome packaging mechanism relies on the redundant and plastic network of RNA-RNA and potentially RNA-nucleoprotein interactions. Homologous gene segments of IAV compete for incorporation into virions and segment containing matched packaging sequences relative to the background of the virus is packaged preferentially

Fig. 2

A model for IAV life cycle. IAVs enter host cells by binding the cell surface receptors containing sialic acid. The vRNPs are released into the cytoplasm after the endocytosis and fusion of the viral and endosomal membranes. The incoming vRNAs of IAV remain associated until they are imported into the nuclei of infected cells. The vRNA replicates and transcribes in the nuclei of infected cells and are transported as vRNPs. After exporting from the nucleus, more than one vRNP assembled en route to the plasma membrane and exported from the nucleus as complex. That is, vRNPs together with the Rab11 protein are recruited to the tubulated endoplasmic reticulum (ER) that on irregularly coated vesicles (ICVs). The ICVs loaded with vRNP and Rab11 then bud from the ER and possibly transferred to the plasma membrane. At the final stage, the vRNPs are interconnected at the budding tip of the virion and are oriented perpendicularly. The progeny virions are then released by enzymatic cleavage of the viral receptor mediated by NA protein

Fig. 3

Schematic diagram of the sequences involved in the packaging of influenza A viruses. All segments are shown in the negative-sense orientation and are numbered according to the conventional representation from 3′ to 5′. The sequences necessary for the incorporation of each segment are color-coded and the references plus the corresponding viral strains are listed on the right