Host Single Nucleotide Polymorphisms Modulating Influenza A Virus Disease in Humans

Abstract

A large number of human genes associated with viral infections contain single nucleotide polymorphisms (SNPs), which represent a genetic variation caused by the change of a single nucleotide in the DNA sequence. SNPs are located in coding or non-coding genomic regions and can affect gene expression or protein function by different mechanisms. Furthermore, they have been linked to multiple human diseases, highlighting their medical relevance. Therefore, the identification and analysis of this kind of polymorphisms in the human genome has gained high importance in the research community, and an increasing number of studies have been published during the last years. As a consequence of this exhaustive exploration, an association between the presence of some specific SNPs and the susceptibility or severity of many infectious diseases in some risk population groups has been found. In this review, we discuss the relevance of SNPs that are important to understand the pathology derived from influenza A virus (IAV) infections in humans and the susceptibility of some individuals to suffer more severe symptoms. We also discuss the importance of SNPs for IAV vaccine effectiveness.

Keywords: Influenza A virus (IAV); Influenza vaccine; innate immunity; single nucleotide polymorphisms (SNPs).

Figure 1

Influenza A virus structure and genome organization. (A) Virion structure: Influenza A viruses include a lipid envelope containing the two viral glycoproteins (HA, green and NA, purple). The ion channel M2 (red) protein is also located in the membrane. Under the viral bilayer is located a protein layer composed of the M1 (light blue) protein, and the NEP (yellow). Inside the virion are located the eight vRNA segments coated by the NP (pink) as viral vRNP complexes and associated with the viral polymerase complex made of the three polymerase subunits PB2 (red), PB1 (blue) and PA (gray). Viral components in the vRNP and in the viral particle are indicated. (B) Genome organization: Influenza A virus contains eight ss, negative-sense, viral RNA segments (PB2, PB1, PA, HA, NP, NA, M, and NS). Each viral segment contains non-coding regions (NCR, black) and the packaging signals (PKS, gray) at the 3′ and 5′ termini in each of the viral segments.

Figure 2

Single nucleotide polymorphisms (SNPs). (A) An SNP is a variation on a single nucleotide which may occur at some specific point in the genome and that causes variations in DNA sequences between members of the same species. (B) Types of SNPs: DNA variation can be located in non-coding or coding regions. SNPs within a coding sequence can be synonymous if they do not produce an amino acid change (silent mutation), or non-synonymous if they affect the protein sequence. Non-synonymous changes can be divided into missense (producing an amino acid change in the protein) or nonsense (producing a truncated or longer protein).