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14 | Perez et al.
As a result, vRNP (viral ribonucleoprotein capsids) trafficking is Together these bird groups show the greatest diversity of IAV
up-regulated which leads to the synthesis of more viral protein, subtypes, comprising all the HA subtypes (H1–H16) and all the
genome and viral particles formation. The interaction between NA subtypes (N1–N9) (Alexander, 2000). Thus, IAV in many
NP and the host antiapoptotic protein Clusterin (CLU) can trig- different H and N combinations have been isolated in nature.
ger the intrinsic apoptotic pathway in human airway epithelial Theoretically, 144 H and N subtype combinations are possible,
cells. This interaction is highly conserved, mediated through but not all have been isolated from birds in nature, suggesting a
β-chain of the CLU protein and does not involve other IAV potential bias given by the requirement of balanced HA and NA
pro-apoptotic proteins. CLU prevents induction of the intrinsic activities and/or other virus and host-specific factors. A list of
apoptosis pathway by binding to Bax and inhibiting its movement major avian groups and the subtype combinations isolated from
into the mitochondria. Therefore, expression of IAV NP reduced each one is provided in Table 1.3 based on IAV sequenced data
the association between CLU and Bax in mammalian cells (Trip- deposited in the Influenza Research Database (www.fludb.org).
athi et al., 2013). It must be noted that many countries around the world do not
have sufficient resources in place nor the regulatory authority
to investigate and report the presence and prevalence of IAVs in
Natural hosts and host range natural and non-natural hosts. Thus, reports are likely incomplete
Wild aquatic birds of the orders Anseriformes (ducks) and and biased towards the notifiable subtypes, H5 and H7.
Charadriiformes (shorebirds and gulls) are considered the natural Replication of IAVs in wild waterfowl and shorebirds occurs
hosts and major reservoir for IAVs (Fig. 1.4) (Alexander, 2000). primarily in the intestinal tract and occasionally in the respiratory
Figure 1.4 Natural hosts and interspecies transmission routes of influenza A viruses.
Table 1.3 Number of IAV strains reported in IRD, by bird taxonomic order (n = 23,431 strains)
Order Family Strains*
Anseriformes Anatidae (ducks, geese, and waterfowl) 12,372
Charadriiformes Alcidae (auks, murres, and puffins) 1862
Burhinidae (thick-knees)
Charadriidae (plovers and lapwings)
Haematopodidae (oystercatchers)
Laridae (gulls, terns, and skimmers)
Recurvirostridae (stilts and avocets)
Scolopacidae (sandpipers and allies)
Galliformes Numididae (guineafowl) 8221
Phasianidae (pheasants, grouse, and allies)