RESUMEN
We designed a participatory monitoring program for the capercaillie population in the French Pyrenees based on lek censuses conducted during the breeding season. This program was implemented by a consortium of stakeholders interested in the conservation of French galliforms. The program, carried out since 2010, relied on a dual frame sampling approach: The first sampled frame was the list of all known leks in the study area. We distinguished two types of known leks: leks known to be active before the onset of the program (with at least one cock detected since 2000) and leks with an indeterminate activity status at the time of the onset of the program. The monitoring program also accounted for the existence of leks that were unknown due mainly to incomplete expert knowledge. We therefore built a complementary area frame by discretizing the study area into a set of 4-km2 grid cells. These cells were then sampled and searched to find unknown leks. When unknown leks were found, cock censuses were organized. An additional field experiment allowed us to estimate the detection probability of unknown leks during these cell searches. We then fitted two hierarchical models: (i) An N-mixture model fitted to the lek census data set allowed us to estimate the mean number of cocks on the three types of leks (known active, known indeterminate, and unknown leks); and (ii) another model fitted to the cell search data set allowed us to estimate the number of unknown leks in the studied mountain range. By multiplying the estimated mean numbers of cocks associated with the three types of leks by the number of leks of each type (an estimated value in the case of unknown leks), we obtained estimates of the total numbers of cocks on all leks at different spatial scales in the study area every 2 years. Our model suggests that the capercaillie cock population was stable from 2010 to 2017 over the whole range but decreased slightly in the foothill area and western part, a decrease that worsened in 2018-2019.
Asunto(s)
Densidad de Población , ProbabilidadRESUMEN
Rabbit hemorrhagic disease virus (RHDV) and European brown hare syndrome virus (EBHSV) are two lagoviruses from the family Caliciviridae that cause fatal diseases in two leporid genera, Oryctolagus and Lepus, respectively. In the last few years, several examples of host jumps of lagoviruses among leporids were recorded. In addition, a new pathogenic genotype of RHDV emerged, and many nonpathogenic strains of lagoviruses have been described. The molecular mechanisms behind host shifts and the emergence of virulence are unknown. Since RHDV uses glycans of the histo-blood group antigen type as attachment factors to initiate infection, we studied if glycan specificities of the new pathogenic RHDV genotype, nonpathogenic lagoviruses, and EBHSV potentially play a role in determining the host range and virulence of lagoviruses. We observed binding to A, B, or H antigens of the histo-blood group family for all strains known to primarily infect European rabbits (Oryctolagus cuniculus), which have recently been classified as GI strains. However, we could not explain the emergence of virulence, since similar glycan specificities were found in several pathogenic and nonpathogenic strains. In contrast, EBHSV, recently classified as GII.1, bound to terminal ß-linked N-acetylglucosamine residues of O-glycans. Expression of these attachment factors in the upper respiratory and digestive tracts in three lagomorph species (Oryctolagus cuniculus, Lepuseuropaeus, and Sylvilagus floridanus) showed species-specific patterns regarding susceptibility to infection by these viruses, indicating that species-specific glycan expression is likely a major contributor to lagovirus host specificity and range.IMPORTANCE Lagoviruses constitute a genus of the family Caliciviridae comprising highly pathogenic viruses, RHDV and EBHSV, that infect rabbits and hares, respectively. Recently, nonpathogenic strains were discovered and new pathogenic strains have emerged. In addition, host jumps between lagomorphs have been observed. The mechanisms responsible for the emergence of pathogenicity and host species range are unknown. Previous studies showed that RHDV strains attach to glycans expressed in the upper respiratory and digestive tracts of rabbits, the likely portals of virus entry. Here, we studied the glycan-binding properties of novel pathogenic and nonpathogenic strains looking for a link between glycan binding and virulence or between glycan specificity and host range. We found that glycan binding did not correlate with virulence. However, expression of glycan motifs in the upper respiratory and digestive tracts of lagomorphs revealed species-specific patterns associated with the host ranges of the virus strains, suggesting that glycan diversity contributes to lagovirus host ranges.
Asunto(s)
Infecciones por Caliciviridae/virología , Virus de la Enfermedad Hemorrágica del Conejo/fisiología , Lagomorpha/virología , Lagovirus/fisiología , Polisacáridos/metabolismo , Virulencia , Acoplamiento Viral , Animales , Infecciones por Caliciviridae/metabolismo , Susceptibilidad a Enfermedades , Liebres , Lagomorpha/clasificación , Lagomorpha/metabolismo , Filogenia , Conejos , Especificidad de la EspecieRESUMEN
We report the full genome sequence of the non-pathogenic rabbit lagovirus Lagovirus europaeus/GI.3/O cun/FR/2006/06-11 (GI.3/06-11), collected from a healthy French domestic rabbit in 2006, and initially described as 06-11 strain. The sequence reveals a genomic organization similar to lagoviruses. It was 7,436 bases long and contained two open reading frames (ORF). A dipeptide variation at the potential p23/2C-like helicase cleavage site (EE instead of ED) was observed, a feature only shared with non-recombinant pathogenic lagoviruses in GI.2 and with two European brown hare syndrome viruses (EBHSV) collected in 1982 in Sweden. GI.3/06-11 has only one initiation codon at the beginning of the ORF2 like the avirulent Italian rabbit calicivirus (RCV) and EBHSV. Previous genetic analyses based on the capsid gene sequences showed that GI.3/06-11 was closer to the RCV and pathogenic lagoviruses GI.1 strains than other lagoviruses. This study, by revealing that GI.3/06-11 genome sequence significantly clustered with pathogenic GI.2 strains, gives prominence of new genetic relationship among lagoviruses and should contribute to understand the emergence of pathogenic strains.
Asunto(s)
Infecciones por Caliciviridae/veterinaria , Caliciviridae/aislamiento & purificación , Genoma Viral , Animales , Caliciviridae/clasificación , Caliciviridae/genética , Infecciones por Caliciviridae/virología , Proteínas de la Cápside/genética , Europa (Continente) , Sistemas de Lectura Abierta , Filogenia , ConejosRESUMEN
Lagoviruses belong to the Caliciviridae family. They were first recognized as highly pathogenic viruses of the European rabbit (Oryctolagus cuniculus) and European brown hare (Lepus europaeus) that emerged in the 1970-1980s, namely, rabbit haemorrhagic disease virus (RHDV) and European brown hare syndrome virus (EBHSV), according to the host species from which they had been first detected. However, the diversity of lagoviruses has recently expanded to include new related viruses with varying pathogenicity, geographic distribution and host ranges. Together with the frequent recombination observed amongst circulating viruses, there is a clear need to establish precise guidelines for classifying and naming lagovirus strains. Therefore, here we propose a new nomenclature based on phylogenetic relationships. In this new nomenclature, a single species of lagovirus would be recognized and called Lagovirus europaeus. The species would be divided into two genogroups that correspond to RHDV- and EBHSV-related viruses, respectively. Genogroups could be subdivided into genotypes, which could themselves be subdivided into phylogenetically well-supported variants. Based on available sequences, pairwise distance cutoffs have been defined, but with the accumulation of new sequences these cutoffs may need to be revised. We propose that an international working group could coordinate the nomenclature of lagoviruses and any proposals for revision.
Asunto(s)
Lagovirus/clasificación , ARN Viral/genética , Terminología como Asunto , Animales , Infecciones por Caliciviridae/virología , Genotipo , Liebres , Lagovirus/genética , Lagovirus/patogenicidad , Filogenia , ConejosRESUMEN
RHDV (rabbit hemorrhagic disease virus), a virulent calicivirus, causes high mortalities in European rabbit populations (Oryctolagus cuniculus). It uses α1,2fucosylated glycans, histo-blood group antigens (HBGAs), as attachment factors, with their absence or low expression generating resistance to the disease. Synthesis of these glycans requires an α1,2fucosyltransferase. In mammals, there are three closely located α1,2fucosyltransferase genes rSec1, rFut2 and rFut1 that arose through two rounds of duplications. In most mammalian species, Sec1 has clearly become a pseudogene. Yet, in leporids, it does not suffer gross alterations, although we previously observed that rabbit Sec1 variants present either low or no activity. Still, a low activity rSec1 allele correlated with survival to an RHDV outbreak. We now confirm the association between the α1,2fucosyltransferase loci and survival. In addition, we show that rabbits express homogenous rFut1 and rFut2 levels in the small intestine. Comparison of rFut1 and rFut2 activity showed that type 2 A, B and H antigens recognized by RHDV strains were mainly synthesized by rFut1, and all rFut1 variants detected in wild animals were equally active. Interestingly, rSec1 RNA levels were highly variable between individuals and high expression was associated with low binding of RHDV strains to the mucosa. Co-transfection of rFut1 and rSec1 caused a decrease in rFut1-generated RHDV binding sites, indicating that in rabbits, the catalytically inactive rSec1 protein acts as a dominant-negative of rFut1. Consistent with neofunctionalization of Sec1 in leporids, gene conversion analysis showed extensive homogenization between Sec1 and Fut2 in leporids, at variance with its limited degree in other mammals. Gene conversion additionally involving Fut1 was also observed at the C-terminus. Thus, in leporids, unlike in most other mammals where it became extinct, Sec1 evolved a new function with a dominant-negative effect on rFut1, contributing to fucosylated glycan diversity, and allowing herd protection from pathogens such as RHDV.
Asunto(s)
Infecciones por Caliciviridae/genética , Fucosiltransferasas/genética , Virus de la Enfermedad Hemorrágica del Conejo/genética , Polimorfismo Genético , Polisacáridos/genética , Animales , Secuencia de Bases , Resistencia a la Enfermedad/genética , Lagomorpha , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Conejos , TransfecciónRESUMEN
Rabbit haemorrhagic disease virus (RHDV) is a lagovirus that causes rabbit haemorrhagic disease (RHD) in European rabbits (Oryctolagus cuniculus). In 2010, a new genotype called RHDV2 emerged in France. It exhibits a larger host range than classical RHDV strains by sporadically infecting different hare species, including the European hare (Lepus europaeus). Phylogenetic analyses revealed that closely related RHDV2 strains circulate locally in both hares and rabbits, and therefore that RHDV2 strains infecting hares do not belong to a lineage that has evolved only in this species. We showed that RHDV2 is widely distributed in France and that it was responsible for more than a third of cases of lagovirus disease in European hare populations in 2015. The oldest RHDV2 positive hare was sampled in November 2013 and we reported two hares co-infected by EBHSV and RHDV2. All together, our results raise important epidemiological and evolutionary issues. In particular, along with the potential emergence of recombinant EBHSV/RHDV2 strains in hares, the enlargement of the host range changes the host population structure of RHDV2 and may alter the impact of the virus on rabbit and hare populations.
Asunto(s)
Infecciones por Caliciviridae/veterinaria , Brotes de Enfermedades/veterinaria , Liebres , Virus de la Enfermedad Hemorrágica del Conejo/genética , Lagovirus/genética , Conejos , Animales , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/virología , Francia/epidemiología , Genotipo , Hígado/virología , Epidemiología Molecular , Filogenia , PrevalenciaRESUMEN
The eastern cottontail (Sylvilagus floridanus) is an American lagomorph. In 1966, it was introduced to Italy, where it is currently widespread. Its ecological niche is similar to those of native rabbits and hares and increasing overlap in distribution brings these species into ever closer contact. Therefore, cottontails are at risk of infection with the two lagoviruses endemically present in Italy: Rabbit Haemorrhagic Disease virus (RHDV) and European Brown Hare Syndrome Virus (EBHSV). To verify the susceptibility of Sylvilagus to these viruses, we analyzed 471 sera and 108 individuals from cottontail populations in 9 provinces of north-central Italy from 1999 to 2012. In total, 15-20% of the cottontails tested seropositive for EBHSV; most titres were low, but some were as high as 1/1280. All the cottontails virologically tested for RHDV and EBHSV were negative with the exception of one individual found dead with hares during a natural EBHS outbreak in December 2009. The cottontail and the hares showed typical EBHS lesions, and the EBHSV strain identified was the same in both species (99.9% identity). To experimentally confirm the diagnosis, we performed two trials in which we infected cottontails with both EBHSV and RHDV. One out of four cottontails infected with EBHSV died of an EBHS-like disease, and the three surviving animals developed high EBHSV antibody titres. In contrast, neither mortality nor seroconversion was detected after infection with RHDV. Taken together, these results suggest that Sylvilagus is susceptible to EBHSV infection, which occasionally evolves to EBHS-like disease; the eastern cottontail could therefore be considered a "spill over" or "dead end" host for EBHSV unless further evidence is found to confirm that it plays an active role in the epidemiology of EBHSV.
Asunto(s)
Infecciones por Caliciviridae/veterinaria , Brotes de Enfermedades/veterinaria , Lagomorpha , Lagovirus/aislamiento & purificación , Animales , Anticuerpos Antivirales/sangre , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/transmisión , Infecciones por Caliciviridae/virología , Ensayo de Inmunoadsorción Enzimática/veterinaria , Femenino , Virus de la Enfermedad Hemorrágica del Conejo/aislamiento & purificación , Especies Introducidas , Italia/epidemiología , Masculino , Estaciones del AñoRESUMEN
The role of maternal antibodies is to protect newborns against acute early infection by pathogens. This can be achieved either by preventing any infection or by allowing attenuated infections associated with activation of the immune system, the two strategies being based on different cost/benefit ratios. We carried out an epidemiological survey of myxomatosis, which is a highly lethal infectious disease, in two distant wild populations of rabbits to describe the epidemiological pattern of the disease. Detection of specific IgM and IgG enabled us to describe the pattern of immunity. We show that maternal immunity attenuates early infection of juveniles and enables activation of their immune system. This mechanism associated with steady circulation of the myxoma virus in both populations, which induces frequent reinfections of immune rabbits, leads to the maintenance of high immunity levels within populations. Thus, myxomatosis has a low impact, with most infections being asymptomatic. This work shows that infection of young rabbits protected by maternal antibodies induces attenuated disease and activates their immune system. This may play a major role in reducing the impact of a highly lethal disease when ecological conditions enable permanent circulation of the pathogen.
Asunto(s)
Inmunidad Adaptativa , Inmunidad Colectiva , Myxoma virus/fisiología , Mixomatosis Infecciosa/inmunología , Conejos , Factores de Edad , Animales , Anticuerpos Antivirales/sangre , Ensayo de Inmunoadsorción Enzimática/veterinaria , Femenino , Francia/epidemiología , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Mixomatosis Infecciosa/epidemiología , Mixomatosis Infecciosa/virologíaRESUMEN
Shah and colleagues [...].
Asunto(s)
Filogeografía , Filogenia , Genoma Viral , Humanos , AnimalesRESUMEN
Rabbit Hemorrhagic disease virus (RHDV), a calicivirus of the Lagovirus genus, and responsible for rabbit hemorrhagic disease (RHD), kills rabbits between 48 to 72 hours post infection with mortality rates as high as 50-90%. Caliciviruses, including noroviruses and RHDV, have been shown to bind histo-blood group antigens (HBGA) and human non-secretor individuals lacking ABH antigens in epithelia have been found to be resistant to norovirus infection. RHDV virus-like particles have previously been shown to bind the H type 2 and A antigens. In this study we present a comprehensive assessment of the strain-specific binding patterns of different RHDV isolates to HBGAs. We characterized the HBGA expression in the duodenum of wild and domestic rabbits by mass spectrometry and relative quantification of A, B and H type 2 expression. A detailed binding analysis of a range of RHDV strains, to synthetic sugars and human red blood cells, as well as to rabbit duodenum, a likely gastrointestinal site for viral entrance was performed. Enzymatic cleavage of HBGA epitopes confirmed binding specificity. Binding was observed to blood group B, A and H type 2 epitopes in a strain-dependent manner with slight differences in specificity for A, B or H epitopes allowing RHDV strains to preferentially recognize different subgroups of animals. Strains related to the earliest described RHDV outbreak were not able to bind A, whereas all other genotypes have acquired A binding. In an experimental infection study, rabbits lacking the correct HBGA ligands were resistant to lethal RHDV infection at low challenge doses. Similarly, survivors of outbreaks in wild populations showed increased frequency of weak binding phenotypes, indicating selection for host resistance depending on the strain circulating in the population. HBGAs thus act as attachment factors facilitating infection, while their polymorphism of expression could contribute to generate genetic resistance to RHDV at the population level.
Asunto(s)
Antígenos de Grupos Sanguíneos/genética , Infecciones por Caliciviridae/veterinaria , Virus de la Enfermedad Hemorrágica del Conejo/genética , Virus de la Enfermedad Hemorrágica del Conejo/patogenicidad , Animales , Australia , Antígenos de Grupos Sanguíneos/metabolismo , Infecciones por Caliciviridae/sangre , Infecciones por Caliciviridae/virología , ADN Viral/genética , Duodeno/virología , Epítopos/metabolismo , Hemaglutinación por Virus , Inmunohistoquímica , Espectrometría de Masas , Fenotipo , Filogenia , Unión Proteica , ConejosRESUMEN
Since summer 2010, numerous cases of Rabbit Haemorrhagic Disease (RHD) have been reported in north-western France both in rabbitries, affecting RHD-vaccinated rabbits, and in wild populations. We demonstrate that the aetiological agent was a lagovirus phylogenetically distinct from other lagoviruses and which presents a unique antigenic profile. Experimental results show that the disease differs from RHD in terms of disease duration, mortality rates, higher occurrence of subacute/chronic forms and that partial cross-protection occurs between RHDV and the new RHDV variant, designated RHDV2. These data support the hypothesis that RHDV2 is a new member of the Lagovirus genus. A molecular epidemiology study detected RHDV2 in France a few months before the first recorded cases and revealed that one year after its discovery it had spread throughout the country and had almost replaced RHDV strains. RHDV2 was detected in continental Italy in June 2011, then four months later in Sardinia.
Asunto(s)
Infecciones por Caliciviridae/veterinaria , Virus de la Enfermedad Hemorrágica del Conejo/clasificación , Virus de la Enfermedad Hemorrágica del Conejo/genética , Conejos , Proteínas Estructurales Virales/genética , Secuencia de Aminoácidos , Animales , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/virología , Ensayo de Inmunoadsorción Enzimática/veterinaria , Francia/epidemiología , Pruebas de Hemaglutinación/veterinaria , Virus de la Enfermedad Hemorrágica del Conejo/química , Virus de la Enfermedad Hemorrágica del Conejo/metabolismo , Datos de Secuencia Molecular , Filogenia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria , Alineación de Secuencia/veterinaria , Proteínas Estructurales Virales/química , Proteínas Estructurales Virales/metabolismoRESUMEN
Hepatitis E virus (HEV) strains from rabbits indicate that these mammals may be a reservoir for HEVs that cause infection in humans. To determine HEV prevalence in rabbits and the strains' genetic characteristics, we tested bile, liver, and additional samples from farmed and wild rabbits in France. We detected HEV RNA in 7% (14/200) of bile samples from farmed rabbits (in 2009) and in 23% (47/205) of liver samples from wild rabbits (in 2007-2010). Full-length genomic sequences indicated that all rabbit strains belonged to the same clade (nucleotide sequences 72.2%-78.2% identical to HEV genotypes 1-4). Comparison with HEV sequences of human strains and reference sequences identified a human strain closely related to rabbit strain HEV. We found a 93-nt insertion in the X domain of open reading frame 1 of the human strain and all rabbit HEV strains. These findings indicate that the host range of HEV in Europe is expanding and that zoonotic transmission of HEV from rabbits is possible.
Asunto(s)
Virus de la Hepatitis E/genética , Hepatitis E/veterinaria , Conejos/virología , Zoonosis/virología , Crianza de Animales Domésticos , Animales , Animales Salvajes/virología , Bilis/virología , Francia/epidemiología , Genotipo , Hepatitis E/epidemiología , Hepatitis E/transmisión , Hepatitis E/virología , Virus de la Hepatitis E/clasificación , Virus de la Hepatitis E/aislamiento & purificación , Humanos , Hígado/virología , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Filogenia , ARN Viral/genética , Análisis de Secuencia de ADN , Zoonosis/transmisiónRESUMEN
First recognized as highly pathogenic viruses, hare lagoviruses belonging to genotype GII.1 (EBHSV) infect various Lepus species. Genetically distinct benign lagoviruses (Hare Calicivirus, HaCV) have recently been identified but few data have been available so far on these strains. The analysis of 199 samples from hunted hares collected throughout France allowed the detection of 20 HaCV and showed that they were widely distributed in this country. Ten HaCV capsid protein gene sequences were characterized. A first HaCV capsid protein structural model was proposed, revealing a global structure similar to that of a pathogenic GII.1 strain. The HaCV sequences showed an even higher genetic diversity than previously appreciated, with the characterization of two genotypes (GII.2, GII.3) and several additional putative genotypes. The most recent common ancestor for HaCV VP60 gene was estimated to be much older than that for GII.1 pathogenic strains. These results give new insights into the phylogenetic relationships of HaCV within the Lagovirus genus.
Asunto(s)
Variación Genética , Liebres/virología , Lagovirus/genética , Animales , Evolución Biológica , Infecciones por Caliciviridae/veterinaria , Infecciones por Caliciviridae/virología , Francia , Lagovirus/clasificación , Lagovirus/aislamiento & purificación , FilogeniaRESUMEN
Rabbit haemorrhagic disease is a viral disease that emerged in the 1980s and causes high mortality and morbidity in the European rabbit (Oryctolagus cuniculus). In 2010, a new genotype of the rabbit haemorrhagic disease virus emerged and replaced the former circulating Lagovirus europaeus/GI.1 strains. Several recombination events have been reported for the new genotype Lagovirus europaeus/GI.2, with pathogenic (variants GI.1a and GI.1b) and benign (genotype GI.4) strains that served as donors for the non-structural part while GI.2 composed the structural part; another recombination event has also been described at the p16/p23 junction involving GI.4 strains. In this study, we analysed new complete coding sequences of four benign GI.3 strains and four GI.2 strains. Phylogenetic and recombination detection analyses revealed that the first GI.2 strains, considered as non-recombinant, resulted from a recombination event between GI.3 and GI.2, with GI.3 as the major donor for the non-structural part and GI.2 for the structural part. Our results indicate that recombination contributed to the emergence, persistence and dissemination of GI.2 as a pathogenic form and that all described GI.2 strains so far are the product of recombination. This highlights the need to study full-genomic sequences of lagoviruses to understand their emergence and evolution.
Asunto(s)
Infecciones por Caliciviridae/veterinaria , Virus de la Enfermedad Hemorrágica del Conejo/genética , Filogenia , Recombinación Genética , Animales , Infecciones por Caliciviridae/virología , Cápside , Francia , Genoma Viral , Genotipo , Funciones de Verosimilitud , Conejos/virologíaRESUMEN
Recombination is one of the major sources of genetic variation in viruses. RNA viruses, such as rabbit hemorrhagic disease virus (RHDV), are among the viruses with the highest recombination rates. Several recombination events have been described for RHDV, mostly as a consequence of their genomic architecture. Here, we undertook phylogenetic and recombination analyses of French and Swedish RHDV strains from 1994 to 2016 and uncovered a new intergenotypic recombination event. This event occurred in the late 1990s/early 2000s and involved nonpathogenic GI.3 strains as donors for the nonstructural part of the genome of these recombinants, while pathogenic GI.1d strains contributed to the structural part. These GI.3P-GI.1d recombinant strains did not entirely replace GI.1d (nonrecombinant) strains, but became the dominant strains in France and Sweden, likely due to a fitness advantage associated with this genomic architecture. GI.3P-GI.1d (P stands for polymerase) strains persisted until 2013 and 2016 in Sweden and France, respectively, and cocirculated with the new genotype GI.2 in France. Since strains from the first GI.2 outbreaks were GI.3P-GI.2, we hypothesize that GI.3P-GI.1d could be the parental strain. Our results confirm the outstanding recombination ability of RHDV and its importance in the evolution of lagoviruses, which was only revealed by studying complete genomic sequences.
Asunto(s)
Enfermedades de los Animales/epidemiología , Enfermedades de los Animales/virología , Infecciones por Caliciviridae/veterinaria , Virus de la Enfermedad Hemorrágica del Conejo/clasificación , Virus de la Enfermedad Hemorrágica del Conejo/genética , Recombinación Genética , Animales , Animales Salvajes , Evolución Molecular , Francia/epidemiología , Genoma Viral , Genotipo , Historia del Siglo XX , Filogenia , ARN Viral , Estudios Retrospectivos , Suecia/epidemiologíaRESUMEN
RHDV (rabbit hemorrhagic disease virus) is a highly virulent calicivirus that has become a major cause of mortality in wild rabbit populations (Oryctolagus cuniculus). It binds to the histo-blood group antigen (HBGA) H type 2 which requires an alpha1,2fucosyltransferase for its synthesis. In rabbit, three alpha1,2fucosyltransferases genes are known, Fut1, Fut2, and Sec1. Nonfunctional alleles at any of these loci could potentially confer resistance to RHDV, similar to human FUT2 alleles that determine the nonsecretor phenotype and resistance to infection by various NoV strains. In this study, we looked for the presence of H type 2 on buccal epithelial cells of wild rabbits from two geographic areas under RHDV pressure and from one RHDV-free area. Some animals with diminished H type 2 expression were found in the three populations (nonsecretor-like phenotype). Their frequency markedly increased according to the RHDV impact, suggesting that outbreaks selected survivors with low expression of the virus ligand. Polymorphisms of the Fut1, Fut2, and Sec1 coding regions were determined among animals that either died or survived outbreaks. The Fut2 and Sec1 genes presented a high polymorphism and the frequency of one Sec1 allele was significantly elevated, over 6-fold, among survivors. Sec1 enzyme variants showed either moderate, low, or undetectable catalytic activity, whereas all variant Fut2 enzymes showed strong catalytic activity. This functional analysis of the enzymes encoded by each Fut2 and Sec1 allele suggests that the association between one Sec1 allele and survival might be explained by a deficit of alpha1,2fucosyltransferase expression rather than by impaired catalytic activity.
Asunto(s)
Sistema del Grupo Sanguíneo ABO/metabolismo , Fucosiltransferasas/genética , Virus de la Enfermedad Hemorrágica del Conejo , Polimorfismo Genético , Alelos , Animales , Secuencia de Bases , Datos de Secuencia Molecular , Conejos , Galactósido 2-alfa-L-FucosiltransferasaRESUMEN
Several studies have shown that classical results of microparasite evolution could not extend to the case where the host species shows an important spatial structure. Rabbit haemorrhagic disease virus (RHDV), responsible for rabbit haemorrhagic disease (RHD), which recently emerged in rabbits, has strains within a wide range of virulence, thus providing an interesting example of competition between strains infecting a host species with a metapopulation structure. In addition, rabbits may show a genetic diversity regarding RHDV susceptibility. In the present paper we use the example of the rabbit-RHDV interaction to study the competition between strains of a same microparasite in a host population that is both spatially and genetically structured. Using metapopulation models we show that the evolution of the microparasite is guided by a trade-off between its capacity to invade subpopulations potentially infected by other strains and its capacity to persist within the subpopulation. In such a context, host genetic diversity acts by reducing the number of hosts susceptible to each strain, often favouring more persistent-and generally less virulent-strains. We also show that even in a stochastic context where host genes regularly go locally extinct, the microparasite pressure helps maintain the genetic diversity in the long term while reinforcing gene loss risk in the short term. Finally, we study how different demographic and epidemiologic parameters affect the coevolution between the rabbit and RHDV.
Asunto(s)
Evolución Biológica , Infecciones por Caliciviridae/transmisión , Virus de la Enfermedad Hemorrágica del Conejo/patogenicidad , Modelos Estadísticos , Conejos/genética , Animales , Susceptibilidad a Enfermedades , Predisposición Genética a la Enfermedad , Variación Genética , Virus de la Enfermedad Hemorrágica del Conejo/genética , Interacciones Huésped-Parásitos , Dinámica Poblacional , Conejos/virología , VirulenciaRESUMEN
In the 1950s the myxoma virus was released into European rabbit populations in Australia and Europe, decimating populations and resulting in the rapid evolution of resistance. We investigated the genetic basis of resistance by comparing the exomes of rabbits collected before and after the pandemic. We found a strong pattern of parallel evolution, with selection on standing genetic variation favoring the same alleles in Australia, France, and the United Kingdom. Many of these changes occurred in immunity-related genes, supporting a polygenic basis of resistance. We experimentally validated the role of several genes in viral replication and showed that selection acting on an interferon protein has increased the protein's antiviral effect.
Asunto(s)
Adaptación Biológica/genética , Inmunidad Innata/genética , Myxoma virus/inmunología , Mixomatosis Infecciosa/inmunología , Conejos/genética , Conejos/virología , Alelos , Animales , Australia , Evolución Molecular , Francia , Frecuencia de los Genes , Variación Genética , Interferón alfa-2/genética , Interferón alfa-2/inmunología , Mixomatosis Infecciosa/genética , Polimorfismo de Nucleótido Simple , Población , Conejos/inmunología , Reino UnidoRESUMEN
Many diseases are less severe when they are contracted in early life. For highly lethal diseases, such as myxomatosis in rabbits, getting infected early in life can represent the best chance for an individual to survive the disease. For myxomatosis, early infections are attenuated by maternal antibodies. This may lead to the immunisation of the host, preventing the subsequent development of the lethal form of the disease. But early infection of young individuals requires specific demographic and epidemiological contexts, such as a high transmission rate of the pathogen agent. To investigate other factors involved in the impact of such diseases, we have built a stochastic model of a rabbit metapopulation infected by myxomatosis. We show that the impact of the pathogen agent can be reduced by early infections only when the agent has a long local persistence time and/or when the host subpopulations are highly connected. The length of the reproductive period and the duration of acquired immunity are also important factors influencing the persistence of the pathogen and thus, the impact of the disease. Besides confirming the role of classical factors in the persistence of a pathogen agent, such as the size of the subpopulation or the degree of connectivity, our results highlight novel factors that can modulate the impact of diseases whose severity increase with age.