A question of self-preservation : immunopathology in influenza virus infection

Influenza A viruses that circulate normally in the human population cause a debilitating, though generally transient, illness that is sometimes fatal, particularly in the elderly. Severe complications arising from pandemic influenza or the highly pathogenic avian H5N1 viruses are often associated with rapid, massive inflammatory cell infiltration, acute respiratory distress, reactive hemophagocytosis and multiple organ involvement. Histological and pathological indicators strongly suggest a key role for an excessive host response in mediating at least some of this pathology. Here, we review the current literature on how various effector arms of the immune system can act deleteriously to initiate or exacerbate pathological damage in this viral pneumonia. Generally, the same immunological factors mediating tissue damage during the anti-influenza immune response are also critical for efficient elimination of virus, thereby posing a significant challenge in the design of harmless yet effective therapeutic strategies for tackling influenza virus.

Will Wallace’s Line save Australia from avian influenza?

Australia is separated from the Asian faunal realm by Wallace's Line, across which there is relatively little avian migration. Although this does diminish the risk of high pathogenicity avian influenza of Asian origin arriving with migratory birds, the barrier is not complete. Migratory shorebirds, as well as a few landbirds, move through the region on annual migrations to and from Southeast Asia and destinations further north, although the frequency of infection of avian influenza in these groups is low. Nonetheless,high pathogenicity H5N1 has recently been recorded on the island of New Guinea in West Papua in domestic poultry. This event increases interest in the movements of birds between Wallacea in eastern Indonesia, New Guinea, and Australia, particularly by waterbirds. There are frequent but irregular movements of ducks, geese, and other waterbirds across Torres Strait between New Guinea and Australia, including movements to regions in which H5N1 has occurred in the recent past. Although the likelihood of avian influenza entering Australia via an avian vector is presumed to be low, the nature and extent of bird movements in this region is poorly known. There have been five recorded outbreaks of high pathogenicityavian influenza in Australian poultry flocks, all of the H7 subtype. To date, Australia is the only inhabited continent not to have recorded high pathogenicity avian influenza since 1997, and H5N1 has never been recorded. The ability to map risk from high pathogenicity avian influenza to Australia is hampered by the lack of quantitative data on the extent of bird movements between Australia and its northern neighbors.Recently developed techniques offer the promise to fill this knowledge gap.

Surveillance of wild birds for avian influenza virus

Recent demand for increased understanding of avian influenza virus in its natural hosts, together with the development of high-throughput diagnostics, has heralded a new era in wildlife disease surveillance. However, survey design, sampling, and interpretation in the context of host populations still present major challenges. We critically reviewed current surveillance to distill a series of considerations pertinent to avian influenza virus surveillance in wild birds, including consideration of what, when, where, and how many to sample in the context of survey objectives. Recognizing that wildlife disease surveillance is logistically and financially constrained, we discuss pragmatic alternatives for achieving probability-based sampling schemes that capture this host-pathogen system. We recommend hypothesis-driven surveillance through standardized, local surveys that are, in turn, strategically compiled over broad geographic areas. Rethinking the use of existing surveillance infrastructure can thereby greatly enhance our global understanding of avian influenza and other zoonotic diseases.

Effects of infection-induced migration delays on the epidemiology of avian influenza in wild mallard populations

Wild waterfowl populations form a natural reservoir of Avian Influenza (AI) virus, and fears exist that these birds may contribute to an AI pandemic by spreading the virus along their migratory flyways. Observational studies suggest that individuals infected with AI virus may delay departure from migratory staging sites. Here, we explore the epidemiological dynamics of avian influenza virus in a migrating mallard (Anas platyrhynchos) population with a specific view to understanding the role of infection-induced migration delays on the spread of virus strains of differing transmissibility. We develop a host-pathogen model that combines the transmission dynamics of influenza with the migration, reproduction and mortality of the host bird species. Our modeling predicts that delayed migration of individuals influences both the timing and size of outbreaks of AI virus. We find that (1) delayed migration leads to a lower total number of cases of infection each year than in the absence of migration delay, (2) when the transmission rate of a strain is high, the outbreak starts at the staging sites at which birds arrive in the early part of the fall migration, (3) when the transmission rate is low, infection predominantly occurs later in the season, which is further delayed when there is a migration delay. As such, the rise of more virulent AI strains in waterfowl could lead to a higher prevalence of infection later in the year, which could change the exposure risk for farmed poultry. A sensitivity analysis shows the importance of generation time and loss of immunity for the effect of migration delays. Thus, we demonstrate, in contrast to many current transmission risk models solely using empirical information on bird movements to assess the potential for transmission, that a consideration of infection-induced delays is critical to understanding the dynamics of AI infection along the entire flyway.

Host behaviour and physiology underpin individual variation in avian influenza virus infection in migratory Bewick's swans

Individual variation in infection modulates both the dynamics of pathogens and their impact on host populations. It is therefore crucial to identify differential patterns of infection and understand the mechanisms responsible. Yet our understanding of infection heterogeneity in wildlife is limited, even for important zoonotic host-pathogen systems, owing to the intractability of host status prior to infection. Using novel applications of stable isotope ecology and eco-immunology, we distinguish antecedent behavioural and physiological traits associated with avian influenza virus (AIV) infection in free-living Bewick's swans (Cygnus columbianus bewickii). Swans infected with AIV exhibited higher serum δ13C (-25.3 ± 0.4) than their non-infected counterparts (-26.3±0.2). Thus, individuals preferentially foraging in aquatic rather than terrestrial habitats experienced a higher risk of infection, suggesting that the abiotic requirements of AIV give rise to heterogeneity in pathogen exposure. Juveniles were more likely to be infected (30.8% compared with 11.3% for adults), shed approximately 15-fold higher quantity of virus and exhibited a lower specific immune response than adults. Together, these results demonstrate the potential for heterogeneity in infection to have a profound influence on the dynamics of pathogens, with concomitant impacts on host habitat selection and fitness.

Avian influenza from an ecohealth perspective

To understand and better control AI outbreaks, not only is it necessary to understand the biology of influenza viruses but also the natural history of the hosts in which these viruses multiply and the different environments in which the hosts and viruses interact. This includes the anthropogenic factors that have influenced where, whether and how avian influenza (AI) viruses can replicate and transmit between wild birds and poultry, and between poultry and mammals, including factors influencing uptake and application of appropriate control and preventive measures for AI. This disease represents one of the best examples of the need for a ‘One Health’ approach to understand and tackle disease with an increasing need to comprehend and unravel the environmental and ecology drivers that affect the virus host interactions. This forum piece seeks to bring together these aspects through a review of recent outbreaks and how a deeper understanding of all three aspects, the virus, the host and the environment, can help us better manage future outbreaks.

Transfer of maternal antibodies against avian influenza virus in mallards (Anas platyrhynchos)

Maternal antibodies protect chicks from infection with pathogens early in life and may impact pathogen dynamics due to the alteration of the proportion of susceptible individuals in a population. We investigated the transfer of maternal antibodies against avian influenza virus (AIV) in a key AIV host species, the mallard (Anas platyrhynchos). Combining observations in both the field and in mallards kept in captivity, we connected maternal AIV antibody concentrations in eggs to (i) female body condition, (ii) female AIV antibody concentration, (iii) egg laying order, (iv) egg size and (v) embryo sex. We applied maternity analysis to the eggs collected in the field to account for intraspecific nest parasitism, which is reportedly high in Anseriformes, detecting parasitic eggs in one out of eight clutches. AIV antibody prevalence in free-living and captive females was respectively 48% and 56%, with 43% and 24% of the eggs receiving these antibodies maternally. In both field and captive study, maternal AIV antibody concentrations in egg yolk correlated positively with circulating AIV antibody concentrations in females. In the captive study, yolk AIV antibody concentrations correlated positively with egg laying order. Female body mass and egg size from the field and captive study, and embryos sex from the field study were not associated with maternal AIV antibody concentrations in eggs. Our study indicates that maternal AIV antibody transfer may potentially play an important role in shaping AIV infection dynamics in mallards.

Avian influenza infection dynamics under variable climatic conditions, viral prevalence is rainfall driven in waterfowl from temperate, south-east Australia

Understanding Avian Influenza Virus (AIV) infection dynamics in wildlife is crucial because of possible virus spill over to livestock and humans. Studies from the northern hemisphere have suggested several ecological and environmental drivers of AIV prevalence in wild birds. To determine if the same drivers apply in the southern hemisphere, where more irregular environmental conditions prevail, we investigated AIV prevalence in ducks in relation to biotic and abiotic factors in south-eastern Australia. We sampled duck faeces for AIV and tested for an effect of bird numbers, rainfall anomaly, temperature anomaly and long-term ENSO (El-Niño Southern Oscillation) patterns on AIV prevalence. We demonstrate a positive long term effect of ENSO-related rainfall on AIV prevalence. We also found a more immediate response to rainfall where AIV prevalence was positively related to rainfall in the preceding 3-7 months. Additionally, for one duck species we found a positive relationship between their numbers and AIV prevalence, while prevalence was negatively or not affected by duck numbers in the remaining four species studied. In Australia largely non-seasonal rainfall patterns determine breeding opportunities and thereby influence bird numbers. Based on our findings we suggest that rainfall influences age structures within populations, producing an influx of immunologically naïve juveniles within the population, which may subsequently affect AIV infection dynamics. Our study suggests that drivers of AIV dynamics in the northern hemisphere do not have the same influence at our south-east Australian field site in the southern hemisphere due to more erratic climatological conditions.

Avian influenza virus dynamics in Australian wild birds

Understanding avian influenza infection dynamics in wildlife is crucial because of the possibility of virus spill over to livestock and humans. There are still knowledge gaps how different ecological and environmental factors influence infection dynamics in birds. My study highlights the importance of investigating disease dynamics in Australia.

A gel-capture assay for characterizing the sialyl-glycan selectivity of influenza viruses

Sialic acids (SA) usually linked to galactose (Gal) in an α2,6- or α2,3-configuration are considered the main cell receptors for influenza viruses, in particular for their hemagglutinins (HA). The typing of influenza virus HA receptor selectivity is relevant for understanding the transmissibility of avian and swine viruses to the human population. In this study we developed a simple and inexpensive gel-capture assay (GCA) of the influenza virus HA receptor-binding selectivity. Its principle is the binding of soluble influenza virus to pentasaccharide analogs, representatives of receptors of human and avian influenza viruses, immobilized on a gel resin. The human and avian analogs consisted of a sialyllactose-N-tetraose c (LSTc) [Neu5Ac(α2,6)Gal(β1-3)GlcNAc(β1-3)Gal(β1-4)Glc] and a sialyllactose-N-tetraose a (LSTa) [Neu5Ac(α2,3)Gal(β1-3)GlcNAc(β1-3)Gal(β1-4)Glc], respectively. Following equilibration, the unbound virus is washed away and the bound one is assayed via HA by densitometry as a function of the analog concentration. Using GCA, the receptor selectivity of three influenza viruses of different HA subtype was investigated. The results showed that the egg-adapted A/California/07/2009 (H1N1) virus exhibited an avian α2,3-linked LSTa selectivity, however, it retained the ability to bind to the α2,6-linked LSTc human receptor analog. Influenza B virus B/Florida/4/2006 showed α2,6-linked LSTc selectivity and a poor α2,3-linked LSTa avidity. The H3N2 virus A/Wisconsin/15/2009 displayed almost comparable avidity for both receptor analogs with a marginally greater α2,3-linked LSTa avidity. The described assay protocol provides a simple and rapid method for the characterization of influenza virus HA receptor binding selectivity. Keywords: influenza virus; hemagglutinin; receptor; sialyllactose-N-tetraose; gel-capture assay.

Drought-rainfall cycles as potential environmental drivers of fowl plague and Newcastle disease uutbreaks in Australian poultry

Climatic conditions in Australia are erratic and characterised by periods of intense rainfall followed by periods of intense drought. This has considerable impact on the population dynamics and ecology of many Australian species of waterfowl, which are thought to form the reservoir of avian influenza viruses (AIV) but may also be important carriers (and possibly reservoirs) of other diseases (e.g. bursal disease, Newcastle disease). During the wet, waterfowl numbers increase with many serologically naive juveniles entering the population. During the subsequent period of drought, bird densities increase in the few remaining wetlands. We hypothesise that it is during this period of increasing densities of naive birds that the population’s viral prevalence of some infectious diseases may increase dramatically. Indeed, there exists a remarkable and suggestive coincidence between outbreaks of fowl plaque and Newcastle disease in Australian poultry farms and the periods of drought following a very wet period. In other words, we suspect a link between increased risk for disease outbreaks in poultry farms and the hypothesised high in the prevalences of the viruses causing these diseases in waterfowl. Given that poultry farms may provide ideal conditions for development of high-pathogenic strains, there is also a reciprocal risk for wildlife involved during these periods.