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Review
. 2022 Sep 13;3(5):100306.
doi: 10.1016/j.xinn.2022.100306. Epub 2022 Aug 17.

Co-existence and co-infection of influenza A viruses and coronaviruses: Public health challenges

Jing Yang  1 , Yuhuan Gong  1   2 , Chunge Zhang  1   2 , Ju Sun  1 , Gary Wong  2   3 , Weifeng Shi  4 , Wenjun Liu  1   2 , George F Gao  1   2 , Yuhai Bi  1   2
Affiliations
Review

Co-existence and co-infection of influenza A viruses and coronaviruses: Public health challenges

Jing Yang et al. Innovation (Camb). .

Abstract

Since the 20th century, humans have lived through five pandemics caused by influenza A viruses (IAVs) (H1N1/1918, H2N2/1957, H3N2/1968, and H1N1/2009) and the coronavirus (CoV) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). IAVs and CoVs both have broad host ranges and share multiple hosts. Virus co-circulation and even co-infections facilitate genetic reassortment among IAVs and recombination among CoVs, further altering virus evolution dynamics and generating novel variants with increased cross-species transmission risk. Moreover, SARS-CoV-2 may maintain long-term circulation in humans as seasonal IAVs. Co-existence and co-infection of both viruses in humans could alter disease transmission patterns and aggravate disease burden. Herein, we demonstrate how virus-host ecology correlates with the co-existence and co-infection of IAVs and/or CoVs, further affecting virus evolution and disease dynamics and burden, calling for active virus surveillance and countermeasures for future public health challenges.

Keywords: SARS-CoV-2; co-existence; co-infection; coronavirus; influenza A virus; public health challenges.

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Conflict of interest statement

The authors declare no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
The shared host species of influenza A viruses and coronaviruses The reservoir hosts for influenza A viruses (IAVs; aquatic birds) and multiple coronaviruses (CoVs; bats) are highlighted by a dashed circle in blue and orange color, respectively. Dominant IAVs and CoVs isolated in each host species are listed in the text next to the stick figure. Names of IAVs and CoVs are colored in blue and orange, respectively. The same subtypes of IAVs and CoVs related to the pandemics are colored in red.
Figure 2
Figure 2
Time-scaled phylogenies of global H1N1 and H3N2 seasonal IAVs (A) Time-scaled phylogeny of H1N1 seasonal IAVs around the globe. Current seasonal influenza H1N1 viruses derivate from the A(H1N1)2009 pandemic strains and completely replaced the seasonal H1N1 circulating before 2009 with different genetic and antigenic characteristics. (B) Time-scaled phylogeny of H3N2 seasonal IAVs around the globe. The tips in the tree are colored by the clade classification. The red asterisks represent the vaccine strains. The ladder-like evolution dynamics and seasonal epidemics of H1N1 and H3N2 are, to a large extent, attributed to their partial cross-immunity and the acute and short infectious period. Figures are reannotated from Nextstrain (https://nextstrain.org/influenza/, adapted from and courtesy of Creative Commons Attribution Licensing).
Figure 3
Figure 3
Reassortment and recombination facilitate the emergence of novel variants for IAVs and CoVs The novel H7N9 avian influenza virus (AIV) was found to have emerged by reassortment, obtaining the HA and NA genes from viruses circulating in waterfowls and the internal genes from H9N2 AIV circulating in chickens. MERS-CoV lineage 5 was generated by the genetic recombination between lineage 3 and 4 strains.
Figure 4
Figure 4
Cleavage site motif on HA protein of H5 and H7 AIVs (A) Schematic pattern for the HA protein of IAV. The HA protein can be cleaved into HA1 and HA2 subunits at the cleavage site. The receptor-binding domain (RBD) is located in HA1. (B) The amino acid sequences at the cleavage site for H7 AIVs. H7 LP means low pathogenic AIVs, and other H7 strains are highly pathogenic AIVs. (C) The amino acid sequences at cleavage site for H5. The H5 LP is a low pathogenic AIV, and other H5 strains are highly pathogenic AIVs. In the rightmost column, the red colors represent the key basic residues; “/” represents the cleavage position; the residues of insertion mutation are underlined.
Figure 5
Figure 5
Cleavage site motif of the spike protein of SARS-CoV-2, SARS-CoV-2-related viruses, and other human CoVs (A) Schematic pattern for SARS-CoV-2 spike (S) protein. The S protein can be cleaved into S1 and S2 proteins at the S1/S2 junction site. The receptor-binding domain (RBD) is located in S1. (B) The amino acid diversity at cleavage site for prototype type, clinical isolates (isolated by Vero cells), and Vero cell-passaged viruses of SARS-CoV-2 as well as SARS-CoV-2-related viruses. (C) Diversity at cleavage sites for seven human CoVs that have been identified to date. Polybasic amino acid insertions are observed in SARS-CoV-2, MERS-CoV, HCoV-OC43, and HCoV-HKU1.
Figure 6
Figure 6
Cell tropism for SARS-CoV-2 and IAVs and their receptors in the human respiratory system (A) Cell tropism for SARS-CoV-2 and its receptor hACE2 in human lung and trachea. (B) Cell tropism for avian and human influenza viruses and distribution of sialic acid receptors in human lung and trachea. α2-3-SA and α2-6-SA represent the α-2,3 and α-2,6 sialic acid receptors, respectively, with a preference for binding to avian and human influenza viruses. The α2-6-SA and α2-3-SA receptors are mainly located in the upper and lower respiratory tracts of humans, respectively. α2-3-SA and α2-6-SA are also occasionally detected in human nasal mucosa and the lower respiratory tract, respectively. AT1 and AT2 represent type I and type II pneumocytes in the alveoli, respectively.
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