Homo- and Heterosubtypic Immunity to Low Pathogenic Avian Influenza Virus Mitigates the Clinical Outcome of Infection with Highly Pathogenic Avian Influenza H5N8 Clade 2.3.4.4.b in Captive Mallards (Anas platyrhynchos)

Abstract

In this study, we investigated the clinical response, viral shedding, transmissibility, pathologic lesions, and tropism of HPAIV Gs/Gd H5N8 subtype (clade 2.3.4.4b), following experimental infection of three groups of captive mallards (Anas platyrhynchos): (i) fully susceptible, (ii) pre-exposed to low pathogenic avian influenza virus (LPAIV) H5N1 subtype, and (iii) pre-exposed to LPAIV H3N8 subtype. Infection of naïve mallards with HPAIV H5N8 resulted in ~60% mortality, neurological signs, abundant shedding, and transmission to contact ducks, who also became sick and died. High amounts of viral RNA were found in all collected organs, with the highest RNA load recorded in the brain. The IHC examinations performed on tissues collected at 4 and 14 days post-infection (dpi) revealed tropism to nervous tissue, myocardium, respiratory epithelium, and hepatic and pancreatic cells. The mallards pre-exposed to LPAIV H5N1 and challenged with HPAIV H5N8 were asymptomatic and showed a significant reduction of viral RNA shedding, yet still sufficient to cause infection (but no disease) in the contact ducks. The AIV antigen was not detected in organs at 4 and 14 dpi, and microscopic lesions were mild and scarce. Similarly, mallards previously inoculated with LPAIV H3N8 remained healthy after challenge with HPAIV H5N8, but viral RNA was detected in large quantities in swabs and organs, particularly in the early phase of infection. However, in contrast to mallards from group I, the IHC staining yielded negative results at the selected timepoints. The virus was transmitted to contact birds, which remained symptomless but demonstrated low levels of viral RNA shedding and mild- to moderate tissue damage despite negative IHC staining. The results indicate that naïve mallards are highly susceptible to HPAIV H5N8 clade 2.3.4.4b and that homo- and heterosubtypic immunity to LPAIV can mitigate the clinical outcomes of infection.

Avian influenza viruses in wild birds in Canada following incursions of highly pathogenic H5N1 virus from Eurasia in 2021/2022

“…There were also no large-scale mortalities and few HPAIV detections in sick and dead dabbling ducks, corroborating that these species exhibit less morbidity and mortality compared to other Anseriformes (43). Exposure to LPAIVs has the potential to provide some level of heterosubtypic cross-protective immunity against HPAIV (44). Captive studies have demonstrated that pre-exposure to specific LPAIVs can confer partial cross-protective heterosubtypic immunity to other LPAIVs (45–47), as well as HPAIVs (44, 48, 49), which can result in reduced viral loads, duration of shedding, and, in the case of HPAIV, reduced morbidity and mortality.…”

“…Reassortment is a recurring phenomenon among LPAIVs within wild waterfowl populations (64, 65), and H5 subtypes of clades 2.3.4.4 and 2.3.4.4b have demonstrated a high propensity to reassort with LPAIVs (44, 66). The co-circulation of HPAIV and LPAIV among wild bird reservoir species (e.g., dabbling ducks) increases opportunities for mixed infections and the emergence of reassortants (64).…”

“…Exposure to LPAIVs has the potential to provide some level of heterosubtypic cross-protective immunity against HPAIV (44). Captive studies have demonstrated that pre-exposure to specific LPAIVs can confer partial cross-protective heterosubtypic immunity to other LPAIVs (45)(46)(47), as well as HPAIVs (44,48,49), which can result in reduced viral loads, duration of shedding, and, in the case of HPAIV, reduced morbidity and mortality. With their high prevalence of both HPAIV and LPAIV, together with their large population sizes (at least 25 million dabbling ducks; USFWS 2022), dabbling ducks are likely candidates as reservoirs of HPAIV in Canada.…”

Highly Pathogenic Avian Influenza (HPAI) H5 Clade 2.3.4.4b Virus Infection in Birds and Mammals

“…The H5 clade 2.3.4.4b viruses have exhibited novel epidemiological and pathobiological characteristics distinct from other clades. An elevated pathogenicity has been observed in several duck species [93,94], considered as the AIV natural hosts, accompanied by asymptomatic infections in certain dabbling ducks [95][96][97]. Frequent die-offs have been observed, particularly in colony-breeding seabirds [98][99][100][101], which have been attributed to a shift in the HPAI virus epidemiology among waterbirds, resulting in the endemic circulation of these strains [102,103].…”

Weathering the Storm of High Pathogenicity Avian Influenza in Waterbirds

“…For example, as a result of the Mycoplama gallisepticum epizootic in North American House Finches, surviving individuals and populations are resistant to Mycoplasma infection (Bonneaud et al 2019). Studies addressing preexposure of avian influenza have demonstrated that Mallards exposed to LPAI have fewer clinical signs when infected with HPAI compared to those that do not (Tarasiuk et al 2023), which may be a key reason as to why infected Mallards have few disease signs and are able to migrate while infected. Further, long lived species, such as seabirds may retain antibodies for many years, such that both previous LPAI or HPAI infection will be protective (Ramos et al 2014).…”