Long-Term Effect of Serial Infections with H13 and H16 Low-Pathogenic Avian Influenza Viruses in Black-Headed Gulls

Abstract

Infections of domestic and wild birds with low-pathogenic avian influenza viruses (LPAIVs) have been associated with protective immunity to subsequent infection. However, the degree and duration of immunity in wild birds from previous LPAIV infection, by the same or a different subtype, are poorly understood. Therefore, we inoculated H13N2 (A/black-headed gull/Netherlands/7/ 2009) and H16N3 (A/black-headed gull/Netherlands/26/2009) LPAIVs into black-headed gulls (Chroicocephalus ridibundus), their natural host species, and measured the long-term immune response and protection against one or two reinfections over a period of >1 year. This is the typical interval between LPAIV epizootics in wild birds. Reinfection with the same virus resulted in progressively less virus excretion, with complete abrogation of virus excretion after two infections for H13 but not H16. However, reinfection with the other virus affected neither the level nor duration of virus excretion. Virus excretion by immunologically naive birds did not differ in total levels of excreted H13 or H16 virus between first-and second-year birds, but the duration of H13 excretion was shorter for second-year birds. Furthermore, serum antibody levels did not correlate with protection against LPAIV infection. LPAIV-infected gulls showed no clinical signs of disease. These results imply that the epidemiological cycles of H13 and H16 in black-headed gulls are relatively independent from each other and depend mainly on infection of firstyear birds. IMPORTANCELow-pathogenic avian influenza viruses (LPAIVs) circulate mainly in wild water birds but are occasionally transmitted to other species, including humans, where they cause subclinical to fatal disease. To date, the effect of LPAIV-specific immunity on the epidemiology of LPAIV in wild birds is poorly understood. In this study, we investigated the effect of H13 and H16 LPAIV infection in black-headed gulls on susceptibility and virus excretion of subsequent infection with the same or the other virus within the same breeding season and between breeding seasons. These are the only two LPAIV hemagglutinin subtypes predominating in this species. The findings suggest that H13 and H16 LPAIV cycles in black-headed gull populations are independent of each other, indicate the importance of first-year birds in LPAIV epidemiology, and emphasize the need for alternatives to avian influenza virus (AIV)-specific serum antibodies as evidence of past LPAIV infection and correlates of protection against LPAIV infection in wild birds.

Competition between IAV subtypes through heterosubtypic immunity modulates re-infection and antibody dynamics in the mallard reservoir

“…A possible explanation of this inconsistency is that these truncated antibodies neutralize IAV but lack HI activity (20). Our results are in agreement with other studies in both ducks and gulls that reported partial to complete protection against re-infection depending on the viruses, time between infections, host species and age and detection method (9,21,22). The long-term persistence of antibodies after natural infection, artificial challenge or vaccination has been reported in captive birds up to 6 to 9 months post-exposure (23-25) though it is not know which parameters (i.e.…”

“…With equal strength of HA immunity to all subtypes the present antigenic diversity found in wild birds would be unlikely. Surprisingly, the results from H13 and H16 experimental infections in black-headed gulls showed limited cross-immunity between subtypes and suggest independent cycles for these viruses (21).…”

Antibody responses to avian influenza viruses in wild birds broaden with age

“…It has been particularly challenging to quantify changes in acquired immunity with age, because the exact ages of wild-caught birds are usually unknown or because lifespans of many domestic bird species that harbour AIV are too short for meaningful patterns to be discerned. An experimental study of wild-caught gulls reared in captivity showed that exposure to AIV results in increased protection against that strain for at least 1 year [19], suggesting that continual exposure to AIVs could result in better protection with increased age. However, while experimental studies provide important insights under controlled conditions, they may not adequately describe long-term acquisition of immunity in wild populations that are exposed to a diverse range of AIV subtypes over prolonged periods and to other sources of mortality.…”

“…At the population level, seasonal peaks in viral prevalence have been observed following hatching, and attributed to the immunological naivety of the unfledged birds [29]. Immunologically naive birds that are challenged by an AIV have similar shedding patterns and probability of seroconversion, regardless of bird age [19]. It is therefore likely that the age-related patterns of seroprevalence and viral prevalence observed in the wild result from birds gaining immunity to AIV with continual exposure throughout the lifespan, rather than changes in immune function specifically resulting from ageing.…”

Parasites of seabirds: A survey of effects and ecological implications

“…Among the 16 described avian influenza virus hemagglutinin subtypes, H13 and H16 are associated to seabirds . Although low pathogenic virus subtypes do not induce clinical signs of disease (Brown et al, 2012;Verhagen et al, 2015), infection with highly pathogenic avian influenza viruses (H5 and H7 subtypes) can induce severe clinical signs. These subtypes can cause cloudy eyes, ruffled feathers, weakness, a lack of coordination, torticollis, and mortality (Brown et al, 2006).…”