In Vitro Growth, Receptor Usage and Pathogenesis of Feline Morbillivirus in the Natural Host.

Feline morbillivirus (FeMV) is a recently discovered virus belonging to the genus Morbillivirus of the virus family Paramyxoviridae. Often, the virus has been detected in urine of cats with a history of urinary disease and has a worldwide distribution. Currently, it is unclear which receptor the virus uses to enter the target cells. Furthermore, many aspects of FeMV biology in vivo, including tissue tropism, pathogenesis, and virus excretion in the natural host remain unclear. In this study we analyzed the replication of FeMV in various cell lines. Secondly, we tested if the presence of feline SLAMF1 (Signaling Lymphocytic Activation Molecule family 1/CD150, principal entry receptor for other members of the Morbillivirus genus) improved FeMV replication efficiency in vitro. Finally, to elucidate in vivo biology in cats, as a natural host for FeMV, we experimentally infected a group of cats and monitored clinical symptoms, viremia, and excretion of the virus during the course of 56 days. Our study showed that FeMV shares some features with other morbilliviruses like the use of the SLAMF1 receptor. For the first time, experimental infection of SPF cats showed that FeMV does not induce an acute clinical disease like other morbilliviruses but can induce lesions in the kidneys, including tubulointerstitial nephritis. Further investigations are needed to confirm the site and dynamics of replication of FeMV in the urinary tract and the longer-term impact of FeMV-induced lesions on the renal function. Whether FeMV infection can result in chronic kidney disease will require the monitoring of cats over a longer period.

Factors affecting the levels of protection transferred from mother to offspring following immune challenge.

INTRODUCTION: The transfer of antibodies from mother to offspring is key to protecting young animals from disease and can have a major impact on responses to infection and offspring fitness. Such maternal effects also allow young that may be exposed to disease in early life to focus resources on growth and development at this critical period of development. Maternally transferred antibodies are therefore an important source of phenotypic variation in host phenotype as well as influencing host susceptibility and tolerance to infection across generations. It has previously been assumed the transfer of antibodies is passive and invariant and reflects the level of circulating antibody in the mother at the time of transfer. However, whether females may vary in the relative amount of protection transferred to offspring has seldom been explored. RESULTS: Here we show that females differ widely in the relative amount of specific blood antibodies they transfer to the embryonic environment (range 9.2%-38.4% of their own circulating levels) in Chinese painted quail (Coturnix chinensis). Relative transfer levels were unrelated to the size of a female's own immune response. Furthermore, individual females were consistent in their transfer level, both across different stages of their immune response and when challenged with different vaccine types. The amount of antibody transferred was related to female condition, but baseline antibody responses of mothers were not. However, we found no evidence for any trade-offs between the relative amount of antibody transferred with other measures of reproductive investment. CONCLUSIONS: These results suggest that the relative amount of antibodies transferred to offspring can vary significantly and consistently between females. Levels of transfer may therefore be a separate trait open to manipulation or selection with potential consequences for offspring health and fitness in both wild and domesticated populations.

Female blue tits with brighter yellow chests transfer more carotenoids to their eggs after an immune challenge.

Female ornaments are present in many species, and it is more and more accepted that sexual or social selection may lead to their evolution. By contrast, the information conveyed by female ornaments is less well understood. Here, we investigated the links between female ornaments and maternal effects. In birds, an important maternal effect is the transmission of resources, such as carotenoids, into egg yolk. Carotenoids are pigments with antioxidant and immunomodulatory properties that are crucial for females and developing offspring. In blue tits, we evaluated whether ultraviolet (UV)/blue and yellow feather colouration signals a female's capacity to allocate carotenoids to egg yolk. Because mounting an immune response is costly and trade-offs are more detectable under harsh conditions, we challenged the immune system of females before laying and examined the carotenoid level of their eggs afterward. A positive association between feather carotenoid chroma and egg carotenoid level would be expected if yellow colouration signals basal immunity. Alternatively, if female colouration more generally reflects maternal capacity to invest in reproduction under challenging conditions, then other components of colouration (i.e. yellow brightness and UV/blue colouration) could be linked to maternal capacity to invest in eggs. No association between egg carotenoid levels and UV/blue crown colouration or female yellow chest chroma was found; the latter result suggests that yellow colouration does not signal immune capacity at laying in this species. By contrast, we found that, among females that mounted a detectable response to the vaccine, those with brighter yellow chests transmitted more carotenoids into their eggs. This result suggests yellow brightness signals maternal capacity to invest in reproduction under challenging conditions, and that male blue tits may benefit directly from choosing brighter yellow females.

Eggshell spottiness reflects maternally transferred antibodies in blue tits.

Blue-green and brown-spotted eggshells in birds have been proposed as sexual signals of female physiological condition and egg quality, reflecting maternal investment in the egg. Testing this hypothesis requires linking eggshell coloration to egg content, which is lacking for brown protoporphyrin-based pigmentation. As protoporphyrins can induce oxidative stress, and a large amount in eggshells should indicate either high female and egg quality if it reflects the female's high oxidative tolerance, or conversely poor quality if it reflects female physiological stress. Different studies supported either predictions but are difficult to compare given the methodological differences in eggshell-spottiness measurements. Using the blue tit Cyanistes caeruleus as a model species, we aimed at disentangling both predictions in testing if brown-spotted eggshell could reflect the quality of maternal investment in antibodies and carotenoids in the egg, and at improving between-study comparisons in correlating several common measurements of eggshell coloration (spectral and digital measures, spotted surface, pigmentation indices). We found that these color variables were weakly correlated highlighting the need for comparable quantitative measurements between studies and for multivariate regressions incorporating several eggshell-color characteristics. When evaluating the potential signaling function of brown-spotted eggshells, we thus searched for the brown eggshell-color variables that best predicted the maternal transfer of antibodies and carotenoids to egg yolks. We also tested the effects of several parental traits and breeding parameters potentially affecting this transfer. While eggshell coloration did not relate to yolk carotenoids, the eggs with larger and less evenly-distributed spots had higher antibody concentrations, suggesting that both the quantity and distribution of brown pigments reflected the transfer of maternal immune compounds in egg yolks. As yolk antibody concentrations were also positively related to key proxies of maternal quality (egg volume, number, yellow feather brightness, tarsus length), eggshells with larger spots concentrated at their broad pole may indicate higher-quality eggs.

Exposure of black-legged kittiwakes to Lyme disease spirochetes: dynamics of the immune status of adult hosts and effects on their survival.

1. Despite a growing interest in wildlife disease ecology, there is a surprising lack of knowledge about the exposure dynamics of individual animals to naturally circulating infectious agents and the impact of such agents on host life-history traits. 2. The exploration of these questions requires detailed longitudinal data on individual animals that can be captured multiple times during their life but also requires being able to account for several sources of uncertainty, notably the partial observation or recapture of individuals at each sampling occasion. 3. We use a multi-year dataset to (i) assess the potential effect of exposure to the tick-borne agent of Lyme disease, Borrelia burgdorferi sensu lato (Bbsl), on adult apparent survival for one of its natural long-lived hosts, the Black-legged kittiwake (Rissa tridactyla), and (ii) investigate the temporal dynamics of individual immunological status in kittiwakes to infer the rate of new exposure and the persistence of the immune response. Using a multi-event modelling approach, potential uncertainties arising from partial observations were explicitly taken into account. 4. The potential impact of Bbsl on kittiwake survival was also evaluated via an experimental approach: the apparent survival of a group of breeding birds treated with an antibiotic was compared with that of a control group. 5. No impact of exposure to Bbsl was detected on adult survival in kittiwakes, in either observational or experimental data. 6. An annual seroconversion rate (from negative to positive) of 1·5% was estimated, but once an individual became seropositive, it remained so with a probability of 1, suggesting that detectable levels of anti-Bbsl antibodies persist for multiple years. 7. These results, in combination with knowledge on patterns of exposure to the tick vector of Bbsl, provide important information for understanding the spatio-temporal nature of the interaction between this host and several of its parasites. Furthermore, our analyses highlight the utility of capture-mark-recapture approaches handling state uncertainty for disease ecology studies.

Drug treatment of malaria infections can reduce levels of protection transferred to offspring via maternal immunity.

Maternally transferred immunity can have a fundamental effect on the ability of offspring to deal with infection. However, levels of antibodies in adults can vary both quantitatively and qualitatively between individuals and during the course of infection. How infection dynamics and their modification by drug treatment might affect the protection transferred to offspring remains poorly understood. Using the rodent malaria parasite Plasmodium chabaudi, we demonstrate that curing dams part way through infection prior to pregnancy can alter their immune response, with major consequences for offspring health and survival. In untreated maternal infections, maternally transferred protection suppressed parasitaemia and reduced pup mortality by 75 per cent compared with pups from naïve dams. However, when dams were treated with anti-malarial drugs, pups received fewer maternal antibodies, parasitaemia was only marginally suppressed, and mortality risk was 25 per cent higher than for pups from dams with full infections. We observed the same qualitative patterns across three different host strains and two parasite genotypes. This study reveals the role that within-host infection dynamics play in the fitness consequences of maternally transferred immunity. Furthermore, it highlights a potential trade-off between the health of mothers and offspring suggesting that anti-parasite treatment may significantly affect the outcome of infection in newborns.

Seabirds and the circulation of Lyme borreliosis bacteria in the North Pacific.

Seabirds act as natural reservoirs to Lyme borreliosis spirochetes and may play a significant role in the global circulation of these pathogens. While Borrelia burgdorferi sensu lato (Bbsl) has been shown to occur in ticks collected from certain locations in the North Pacific, little is known about interspecific differences in exposure within the seabird communities of this region. We examined the prevalence of anti-Bbsl antibodies in 805 individuals of nine seabird species breeding across the North Pacific. Seroprevalence varied strongly among species and locations. Murres (Uria spp.) showed the highest antibody prevalence and may play a major role in facilitating Bbsl circulation at a worldwide scale. Other species showed little or no signs of exposure, despite being present in multispecific colonies with seropositive birds. Complex dynamics may be operating in this wide scale, natural host-parasite system, possibly mediated by the host immune system and host specialization of the tick vector.

Maternal transfer of antibodies: raising immuno-ecology issues.

The transfer of antibodies from mother to offspring has broad potential implications in evolutionary ecology, from the adaptive value of maternal effects to the role of transgenerational plasticity in host-parasite interactions. Recent contributions have addressed key issues such as environmental and genetic factors affecting the amount of antibodies transferred and whether maternal antibodies affect offspring immunity, but little is still known about the implications of the maternal transfer of antibodies in natural populations. By its position at the crossroads between population ecology, animal science, medicine and epidemiology, current studies of the role of the maternal transfer of antibodies highlight how research in ecological immunology needs to combine functional and evolutionary approaches while also keeping in mind ecological settings.

Evidence of an interannual effect of maternal immunization on the immune response of juveniles in a long-lived colonial bird.

Little is known about the maternal transfer of antibodies in natural host-parasite systems despite its possible evolutionary and ecological implications. In domestic animals, the maternal transfer of antibodies can enhance offspring survival via a temporary protection against parasites, but it can also interfere with the juvenile immune response to antigens. We tested the functional role of maternal antibodies in a natural population of a long-lived colonial seabird, the kittiwake (Rissa tridactyla), using a vaccine (Newcastle disease virus vaccine) to mimic parasite exposure combined with a cross-fostering design. We first investigated the role of prior maternal exposure on the interannual transmission of Ab to juveniles. We then tested the effect of these antibodies on the juvenile immune response to the same antigen. The results show that specific maternal antibodies were transferred to chicks 1 year after maternal exposure and that these antibodies were functional, i.e. they affected juvenile immunity. These results suggest that the role of maternal antibodies may depend on the timing and pattern of offspring exposure to parasites, along with the patterns of maternal exposure and the dynamics of her immune response. Overall, our approach underlines that although the transgenerational transfer of antibodies in natural populations is likely to have broad implications, the nature of these effects may vary dramatically among host-parasite systems, depending on the physiological mechanisms involved and the ecological context.

Interannual dynamics of antibody levels in naturally infected long-lived colonial birds.

Little is known about the long-term persistence of specific antibodies (Ab) in natural host-parasite systems despite its potential epidemiological and ecological importance. In long-lived species, knowledge of the dynamics of individual immunological profiles can be important not only for interpreting serology results, but also for assessing transmission dynamics and the potential selective pressures acting on parasites. The aim of this paper was to investigate temporal variation in levels of specific Ab against the bacterium Borrelia burgdorferi sensu lato in adults of a long-lived colonial seabird, the Black-legged Kittiwake Rissa tridactyla. In wild populations, adults are naturally exposed each breeding season to a Borrelia vector, the tick Ixodes uriae. Breeding birds were captured during four consecutive breeding seasons, and parasite infestation quantified. Using enzyme-linked immunosorbent assay (ELISA) and immunoblots, we found that the immunological profiles of anti-Borrelia Ab were highly repeatable among years, reflecting the interannual persistence of Ab levels. We nevertheless also observed that year-to-year changes of Ab levels were related to exposure to ticks in the previous year. The long-term persistence of Ab levels may be an important mechanism of individual protection against future exposure to the microparasite. It will also affect the availability of susceptible hosts, and thus the transmission dynamics of the bacterium. These results illustrate the need to consider the dynamics of the immune response in order to better understand the evolutionary ecology of host-parasite interactions in natural populations.