Influenza A virus PB1-F2 protein prolongs viral shedding in chickens lengthening the transmission window

Abstract

Avian influenza is a significant economic burden on the poultry industry in geographical regions where it is enzootic. It also poses a public health concern when avian influenza subtypes infect humans, often with high mortality. Understanding viral genetic factors which positively contribute to influenza A virus (IAV) fitness – infectivity, spread and pathogenesis – is of great importance both for human and livestock health. PB1-F2 is a small accessory protein encoded by IAV and in mammalian hosts has been implicated in a wide range of functions that contribute to increased pathogenesis. In the avian host, the protein has been understudied despite high-level full-length conservation in avian IAV isolates, which is in contrast to the truncations of the PB1-F2 length frequently found in mammalian host isolates. Here we report that the presence of a full-length PB1-F2 protein, from a low pathogenicity H9N2 avian influenza virus, prolongs infectious virus shedding from directly inoculated chickens, thereby enhancing transmission of the virus by lengthening the transmission window to contact birds. As well as extending transmission, the presence of a full-length PB1-F2 suppresses pathogenicity evidenced by an increased minimum lethal dose in embryonated chicken eggs and increasing survival in directly infected birds when compared to a virus lacking an ORF for PB1-F2. We propose that there is a positive pressure to maintain a full-length functional PB1-F2 protein upon infection of avian hosts as it contributes to the effective transmission of IAV in the field.

Improved detection of influenza A virus from blue‐winged teals by sequencing directly from swab material

“…This sample also contained the PB1-F2 S66 marker, which has been associated with increased pathogenicity in mammals (Conenello et al, 2011). All sequenced PB1 segments showed either the 87 or 90 amino acid-long PB1-F2 protein sequence, which is common in isolates from avian species (James et al, 2016). We also found N and T at position 66; interestingly, PB1-F2 T66 was only found in samples (n = 3 samples) sequenced through swab-NGS.…”

Poultry trading behaviours in Vietnamese live bird markets as risk factors for avian influenza infection in chickens

“…Duck farming often involves raising and storing ducks in open bodies of water, which introduces the risk for wild waterfowl to mix with farmed ducks and transmit influenza viruses. In addition, studies have shown longer virus shedding times for LPAI‐infected ducks, up to 11.5 days, compared with LPAI‐infected chickens, up to 6 days (Hénaux & Samuel, ; James et al, ). Therefore, poultry traders with larger numbers of unsold ducks could increase the transmission window for ducks to infect chickens, especially as unsold ducks may have repeated exposures to wild waterfowl when traders store unsold ducks at home.…”

A Global Perspective on H9N2 Avian Influenza Virus

“…Contact transmission relies on the transfer of particles to mucous membranes directly, or via a fomite intermediate. tropism [15,[71][72][73][74][75][76]. One of the key molecular markers that facilitates adaptation of an AIV from wild aquatic birds to poultry is the deletion of amino acids from the stalk domain of NA, which have been shown to mediate the switch to respiratory tropism in chickens [77,78].…”

“…One of the key molecular markers that facilitates adaptation of an AIV from wild aquatic birds to poultry is the deletion of amino acids from the stalk domain of NA, which have been shown to mediate the switch to respiratory tropism in chickens [77,78]. There is good evidence to suggest that many LPAIV strains transmit by the airborne route, the oral-faecal route and the waterborne route [15,75,79]. However, the favoured mechanism of transmission between individuals varies by host species and viral strain.…”