Evolution and Adaptation of the Avian H7N9 Virus into the Human Host.

Andrew T Bisset,Gerard F Hoyne

doi:10.3390/microorganisms8050778

Abstract

Influenza viruses arise from animal reservoirs, and have the potential to cause pandemics. In 2013, low pathogenic novel avian influenza A(H7N9) viruses emerged in China, resulting from the reassortment of avian-origin viruses. Following evolutionary changes, highly pathogenic strains of avian influenza A(H7N9) viruses emerged in late 2016. Changes in pathogenicity and virulence of H7N9 viruses have been linked to potential mutations in the viral glycoproteins hemagglutinin (HA) and neuraminidase (NA), as well as the viral polymerase basic protein 2 (PB2). Recognizing that effective viral transmission of the influenza A virus (IAV) between humans requires efficient attachment to the upper respiratory tract and replication through the viral polymerase complex, experimental evidence demonstrates the potential H7N9 has for increased binding affinity and replication, following specific amino acid substitutions in HA and PB2. Additionally, the deletion of extended amino acid sequences in the NA stalk length was shown to produce a significant increase in pathogenicity in mice. Research shows that significant changes in transmissibility, pathogenicity and virulence are possible after one or a few amino acid substitutions. This review aims to summarise key findings from that research. To date, all strains of H7N9 viruses remain restricted to avian reservoirs, with no evidence of sustained human-to-human transmission, although mutations in specific viral proteins reveal the efficacy with which these viruses could evolve into a highly virulent and infectious, human-to-human transmitted virus.

Highlights

The pandemic potential of the influenza A virus (IAV) is well known, with the most significant impact occurring during the 1918 Spanish Flu, where mortality was estimated between 21.5 million and 100 million [1]
Switching of the viral H7N9 HA specificity to favour human Sialic acid (SA) receptors is likely to have been facilitated by mutation, and it has been shown that a change in the viral HA molecule is a crucial adaptation in the transmissibility of previous pandemic influenza strains [36]
Truncated NA stalks resulted in significantly greater pathogenic infections in mice, compared with that of a full-length NA stalk virus, the naturally occurring 5 amino acid deletion in the NA stalk of H7N9 had no significant impact on NA activity, viral replication or pathogenesis in mice [57]

Summary

Introduction

The pandemic potential of the influenza A virus (IAV) is well known, with the most significant impact occurring during the 1918 Spanish Flu, where mortality was estimated between 21.5 million and 100 million [1]. Switching of the viral H7N9 HA specificity to favour human SA receptors is likely to have been facilitated by mutation, and it has been shown that a change in the viral HA molecule is a crucial adaptation in the transmissibility of previous pandemic influenza strains [36]. An experimental comparison of the glycan receptor binding site for A/Anhui/1/2013 with H3 HA (its phylogenetically closest human-adapted HA) has highlighted the critical importance of S228 in H3 for an amino acid network containing residues S186, T187 and E190 (Figure 4). This approach successfully demonstrated how a combination of amino acid mutations in H7 HA could result in increased specificity of the H7N9 virus to the α-2,6 linked SA receptors on epithelial cells. Other PB2 mutations are known to contribute to replication, enhanced polymerase activity and virulence, and it appears that a virus with multiple PB2 mutations could be appreciably more virulent

Neuraminidase Stalk Truncation Enhances Pathogenicity and Virulence of H7N9

Conclusions