Rapid death of duck cells infected with influenza: a potential mechanism for host resistance to H5N1

Abstract

Aquatic birds are the natural reservoir for most subtypes of influenza A, and a source of novel viruses with the potential to cause human pandemics, fatal zoonotic disease or devastating epizootics in poultry. It is well recognised that waterfowl typically show few clinical signs following influenza A infection, in contrast, terrestrial poultry such as chickens may develop severe disease with rapid death following infection with highly pathogenic avian influenza. This study examined the cellular response to influenza infection in primary cells derived from resistant (duck) and susceptible (chicken) avian hosts. Paradoxically, we observed that duck cells underwent rapid cell death following infection with low pathogenic avian H2N3, classical swine H1N1 and ‘classical' highly pathogenic H5N1 viruses. Dying cells showed morphological features of apoptosis, increased DNA fragmentation and activation of caspase 3/7. Following infection of chicken cells, cell death occurred less rapidly, accompanied by reduced DNA fragmentation and caspase activation. Duck cells produced similar levels of viral RNA but less infectious virus, in comparison with chicken cells. Such rapid cell death was not observed in duck cells infected with a contemporary Eurasian lineage H5N1 fatal to ducks. The induction of rapid death in duck cells may be part of a mechanism of host resistance to influenza A, with the loss of this response leading to increased susceptibility to emergent strains of H5N1. These studies provide novel insights that should help resolve the long-standing enigma of host–pathogen relationships for highly pathogenic and zoonotic avian influenza.

Function of duck RIG-I in induction of antiviral response against IBDV and avian influenza virus on chicken cells

“…4C, middle and bottom). Kuchipudi et al reported that duck cells underwent rapid cell death after infection with a minimally pathogenic avian H2N3, classical swine H1N1, and classical highly pathogenic H5N1 viruses, but the chicken cells underwent cell death less frequently (Kuchipudi et al, 2012). It was here observed that dRIG-I protected chicken cells from ZB07-induced apoptosis.…”

Differences in highly pathogenic avian influenza viral pathogenesis and associated early inflammatory response in chickens and ducks

“…and elevated in the lungs of infected ducks compared with the later induction of apoptosis in infected chickens. Rapid cell death was found in an in vitro study were duck embryo fibroblast cells were infected with HPAI H5N1 (Kuchipudi et al, 2011), which may lead to a reduced number of virus-infected cells in ducks. Another study (Vanderven et al, 2012) describes the rapid induction of antiviral genes involved in antiviral defence and other cellular processes in the lung of H5N1 HPAI-infected ducks at 1 d.p.i.…”

“…Karpala et al (2011b) reported that MDA-5 levels were up-regulated during HPAI infection in chickens, which could indicate that MDA-5 can functionally compensate for the absence of RIG-I (Liniger et al, 2012). Another explanation for the difference in pathogenesis between ducks and chickens could be that a rapid induction of apoptosis in HPAI-infected ducks may be beneficial to the host, whereas delayed apoptosis in chickens may be an advantage for the virus (Kuchipudi et al, 2011).…”

PA from an H5N1 highly pathogenic avian influenza virus activates viral transcription and replication and induces apoptosis and interferon expression at an early stage of infection

“…Apoptosis (programmed cell death) is another mechanism by which cells restrict viral infection including influenza [67]. However, virus-induced apoptosis causes tissue damage, which is one of the mechanisms of influenza pathogenicity [68].…”