One health, multiple challenges: The inter-species transmission of influenza A virus

Abstract

Influenza A viruses are amongst the most challenging viruses that threaten both human and animal health. Influenza A viruses are unique in many ways. Firstly, they are unique in the diversity of host species that they infect. This includes waterfowl (the original reservoir), terrestrial and aquatic poultry, swine, humans, horses, dog, cats, whales, seals and several other mammalian species. Secondly, they are unique in their capacity to evolve and adapt, following crossing the species barrier, in order to replicate and spread to other individuals within the new species. Finally, they are unique in the frequency of inter-species transmission events that occur. Indeed, the consequences of novel influenza virus strain in an immunologically naïve population can be devastating. The problems that influenza A viruses present for human and animal health are numerous. For example, influenza A viruses in humans represent a major economic and disease burden, whilst the poultry industry has suffered colossal damage due to repeated outbreaks of highly pathogenic avian influenza viruses. This review aims to provide a comprehensive overview of influenza A viruses by shedding light on interspecies virus transmission and summarising the current knowledge regarding how influenza viruses can adapt to a new host.

Fig. 1

Reservoirs and inter-species transmission events of low pathogenic avian influenza viruses. Wild birds, domestic birds, pigs, horses, humans and bats maintain their own influenza A viruses (arrow in circle, subtype in bold). Spill-over events occur occasionally, most frequently from wild birds (arrow straight, subtype normal font). *H7N7 virus emerged amongst horses in the 1950s but is currently thought to be extinct.

Fig. 2

Zoonotic events caused by influenza viruses originating from avian species. The countries where avian zoonotic infections were recorded are indicated in shades of red. * provinces of China: Shanghai, Beijing, Hong Kong, Anhui, Fujian, Jiangsu, Jiangxi, Guangdong, Guizhou, Henan, Hunan, Hebei, Shandong, Zheijang. Additionally, two cases were imported to Taiwan from mainland China. The intensity of the colour correlates with the intensity of the reported cases. In brackets are indicated the number of fatalities against the number of confirmed cases.

Fig. 3

Zoonotic events caused by influenza H5N1 viruses. The countries where human cases of H5N1 virus infection were recorded since 1997 are indicated in shades of green. LPDR: Lao People's Democratic Republic. The intensity of the colour correlates with the intensity of the reported cases. In brackets are indicated the number of fatalities against the number of confirmed cases.

Fig. 4

Adaptation of the hemagglutinin protein in mammals. A) Cartoon representation of a model of the trimer structure HA of A/Indonesia/5/2005 (PDB ID: 1JSM). The momomers have different colours for clarity. Highlighted in yellow is the receptor binding site, that facilitates attachment to the sialic acid receptors on the host cell. Mutations in, or in close proximity of the receptor binding site, together with the presence or absence of potential N-linked glycosylation sites, affect the preference and avidity of binding to α2,3-linked or α2,6-linked sialic acid receptors. Amino acids (position 18, 110, 318, 47 (HA2) and 58 (HA2) (H3 numbering), which have been shown to affect HA-stability, and associated transmission in mammals are highlighted in red. B) Influenza virus phenotypes which are associated with adaptation to mammals, shown for non-adapted and adapted avian influenza viruses. Top panel: Attachment of inactivated influenza viruses to ciliated epithelial cells in ferret upper respiratory tract. Bottom panel: acid stability of HA proteins as measured in syncytia formation assays after exposure to indicated pH.

Fig. 5

Adaptation of the polymerase complex. The programme PyMOL was used to assign the indicated subunits PB2, PB1, PA and the influenza A virus promoter in dark grey, grey, light grey and yellow, respectively. Characterized domains, as well as amino acids relevant for airborne transmission between mammals are indicated. The promoter is bound by parts of all three polymerase subunits. The template, as well as the nascent strand exit the polymerase from a cavity, presumably in two different directions. The structural model of A/little yellow-shouldered bat/Guatemala/060/2010 (H17N10) served as a basis (PDB code: 4WSB).

Fig. 6

Zoonotic events caused by influenza viruses originating from mammalian species. The countries where swine zoonotic infections were recorded are indicated in shade of blue. The orange box indicates the only reported human infection with a seal-origin influenza virus. The intensity of the colour correlates with the intensity of the reported cases. In brackets are indicated the number of fatalities against the number of confirmed cases.