Emergence of Pathogenicity in Lagoviruses: Evolution from Pre-existing Nonpathogenic Strains or through a Species Jump?

Esteves, Pedro J.; Abrantes, Joana; Bertagnoli, Stéphane; Cavadini, Patrizia; Gavier‐Widén, Dolores; Guitton, Jean-Sébastien; Llombart‐Bosch, Antonio; Lemaitre, Evelyne; Letty, Jérôme; Lopes, Ana M.; Neimanis, Aleksija; Ruvoën-Clouet, Nathalie; Pendu, Jacques Le; Marchandeau, Stéphane; Gall-Reculé, Ghislaine Le

doi:10.1371/journal.ppat.1005087

Cited by 33 publications

(33 citation statements)

References 92 publications

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“…Additionally, GI.2 has recombined with non‐pathogenic (GI.4) and GI.1b pathogenic forms in the Iberian Peninsula, generating diversity in the circulating lagoviruses (Lopes, Correia et al., ), although recombinant viruses could not be detected with the methods used in this study. Recombination has been proposed as a possible mechanism of emergence of pathogenic lagoviruses (Esteves et al., ; Forrester, Moss, Turner, Schirrmeier, & Gould, ). Therefore, it is likely that GI.2 is continuing to evolve in situ, which makes monitoring of wild rabbit populations crucial, and calls for the need to employ more efficient diagnostic methods (e.g., sequencing).…”

Section: Discussionmentioning

confidence: 99%

“…This new lagovirus was also detected in Lepus capensis , L. corsicanus , L. europaeus and L. timidus (Camarda et al., ; Hall et al., ; Puggioni et al., ; Velarde et al., ), causing a fatal disease in these species. There is enough evidence to suggest that the lagovirus is not derived from any of the classical pathogenic GI.1 forms circulating in Europe; it may rather have recently emerged from a non‐pathogenic form or following a species jump (Esteves et al., ). This new lagovirus was originally designated as “RHDV2” (Le Gall‐Reculé et al., ) or “RHDVb” (Dalton et al., ), although a recently proposed new nomenclature based on phylogenetic relationships designates it as L. europaeus /GI.2, henceforth GI.2 (Le Pendu et al., ).…”

Section: Introductionmentioning

confidence: 99%

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Epidemiology of RHDV2 (Lagovirus europaeus/GI.2) in free-living wild European rabbits in Portugal

Rouco

Abrantes

Serronha

et al. 2017

Transbound Emerg Dis

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As the detection of the first outbreak of a novel aetiological agent of rabbit haemorrhagic disease commonly called RHDV2 or RHDVb (Lagovirus europaeus/GI.2, henceforth GI.2) in France in 2010, the virus rapidly spread throughout continental Europe and nearby islands such as Great Britain, Sardinia, Sicily, the Azores and the Canary Islands among others. The outbreaks of this new lagovirus cause important economic losses in rabbitries, and ecological disruptions by affecting the conservation of rabbit-sensitive top predators. We analysed 550 rabbit carcasses collected in the field between May 2013 and March 2016, to investigate the epidemiology of GI.2 in free-living populations and to perform a comparative analysis with the epidemiology of classical rabbit haemorrhagic disease virus forms (RHDV, henceforth GI.1) in Portugal. Rabbits were sexed, aged and liver and blood samples were collected for subsequent RHDV screening and serology. A total of 172 samples were PCR-positive to GI.2, whereas GI.1 strains were not detected in any of the samples. The outbreaks of GI.2 revealed a marked seasonality, with peaks during the breeding season (November-May). We also found that approximately, one-third of free-ranging European rabbits in Portugal have seroconverted to GI.2. We demonstrate that the GI.2 lagovirus is currently widespread in wild populations in Portugal and is affecting a high proportion of adults and juveniles. Therefore, ongoing monitoring and surveillance are required to assess the effects of GI.2 on wild rabbit populations, its evolution, and to guide management actions aimed at mitigating the impacts of rabbit declines in the ecosystem and in rural economies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Epidemiology of RHDV2 (Lagovirus europaeus/GI.2) in free-living wild European rabbits in Portugal

Rouco

Abrantes

Serronha

et al. 2017

Transbound Emerg Dis

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“…The origins of virulent RHDV have been the subject of debate. A recent hypothesis is that the high virulence of RHDV may stem from a cross-species transmission event, resulting from the repeated translocation of New World lagomorphs into Europe (42). A competing theory is that RHDV evolved from an avirulent (i.e., RCV-A1-like) virus within European rabbits without a species jump (24,30,43).…”

Section: Figmentioning

confidence: 99%

“…Additionally, S. floridanus was bought into Europe in the late 1960s to restock hunting reserves (42), and it is not inconceivable that European rabbits could have been brought back into Europe from Australia for similar reasons.…”

Section: Figmentioning

confidence: 99%

Benign Rabbit Caliciviruses Exhibit Evolutionary Dynamics Similar to Those of Their Virulent Relatives

Mahar

Nicholson

Eden

et al. 2016

J Virol

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Two closely related caliciviruses cocirculate in Australia: rabbit hemorrhagic disease virus (RHDV) and rabbit calicivirus Australia 1 (RCV-A1). RCV-A1 causes benign enteric infections in the European rabbit (Oryctolagus cuniculus) in Australia and New Zealand, while its close relative RHDV causes a highly pathogenic infection of the liver in the same host. The comparison of these viruses provides important information on the nature and trajectory of virulence evolution, particularly as highly virulent strains of RHDV may have evolved from nonpathogenic ancestors such as RCV-A1. To determine the evolution of RCV-A1 we sequenced the full-length genomes of 44 RCV-A1 samples isolated from healthy rabbits and compared key evolutionary parameters to those of its virulent relative, RHDV. Despite their marked differences in pathogenicity and tissue tropism, RCV-A1 and RHDV have evolved in a very similar manner. Both viruses have evolved at broadly similar rates, suggesting that their dynamics are largely shaped by high background mutation rates, and both exhibit occasional recombination and an evolutionary environment dominated by purifying selection. In addition, our comparative analysis revealed that there have been multiple changes in both virulence and tissue tropism in the evolutionary history of these and related viruses. Finally, these new genomic data suggest that either RCV-A1 was introduced into Australia after the introduction of myxoma virus as a biocontrol agent in 1950 or there was drastic reduction of the rabbit population, and hence of RCV-A1 genetic diversity, perhaps coincident with the emergence of myxoma virus. IMPORTANCEThe comparison of closely related viruses that differ profoundly in propensity to cause disease in their hosts offers a powerful opportunity to reveal the causes of changes in virulence and to study how such changes alter the evolutionary dynamics of these pathogens. Here we describe such a novel comparison involving two closely related RNA viruses that cocirculate in Australia, the highly virulent rabbit hemorrhagic disease virus (RHDV) and the nonpathogenic rabbit calicivirus Australia 1 (RCV-A1). Both viruses infect the European rabbit, but they differ in virulence, tissue tropism, and mechanisms of transmission. Surprisingly, and despite these fundamental differences, RCV-A1 and RHDV have evolved at very similar (high) rates and with strong purifying selection. Furthermore, candidate key mutations were identified that may play a role in virulence and/or tissue tropism and therefore warrant further investigation. R evealing the factors that determine the evolution of virulence in viruses and identifying how changes in virulence might impact viral evolutionary dynamics are key queries in the study of infectious disease evolution. Although there is a large body of work on revealing the relationship between virulence and transmissibility, most studies of virulence evolution involve the retrospective analysis of single viruses (1-4). However, the comparison of closely related...

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“…Ważną rolę w interakcjach z receptorami komórek gospodarza może odgrywać najbardziej wyeksponowany powierzchniowo region C. Relacje pomiędzy pozytywną selekcją i antygenowością sugerują udział w ewolucji RHDV mechanizmu zależnego od układu odpornościowego. Z kolei udział kodonu 476, jako części nieciągłej determinanty antygenowej odpowiedzialnej za hemaglutynację podkreśla wpływ tego fragmentu genu na fenotyp wirusa (14), jednakże koncepcja ewolucyjnego przejścia od pierwotnych, niechorobotwórczych wirusów krążących w populacji europejskich zającowatych do formy patogennej nie w pełni wyjaśnia pochodzenie RHDV, EBHSV i RHDV2 (23). Nie tłumaczy też wielokrotnie obserwowanego zjawiska nagłego pojawienia się choroby o bardzo wysokim współczynniku śmier-telności, w krótkim przedziale czasu, w sytuacji, gdy wirusy patogenne i niepatogenne różnią się tak znacznie pod względem filogenetycznym (20% sekwencji nukleotydów genu vp60).…”

Section: Zmienność Wirusa Rhdunclassified

Diversity of RHD virus: epidemiological, diagnostic and immunological importance

Fitzner¹,

Niedbalski²

2017

Medycyna Weterynaryjna

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Summary Rabbit haemorrhagic disease (RHD) was first recognized in Keywords: rabbit haemorrhagic disease (RHD), RHD virus diversity, variants (subtypes)Med. Weter. 2017, 73 (12), 811-818 812 pod nazwą viral heamorrhagic disease of rabbits (VHD) (56), zmienioną później na rabbit haemorrhagic disease (RHD). W Polsce RHD znajduje się w wykazie chorób podlegających obowiązkowi rejestracji (Ustawa z dnia 11 marca 2004 r. o ochronie zdrowia zwierząt oraz o zwalczaniu chorób zakaźnych, zał. 3).Czynnikiem etiologicznym RHD jest wirus krwotocznej choroby królików (rabbit hamorrhagic disease virus -RHDV), rodzaj Lagovirus, rodzina Caliciviridae (59). Bezotoczkowe wiriony RHDV zawierają pojedynczą nić RNA (ok. 7,5 kb) o dodatniej polaryzacji (ss+) zakończoną końcem poly A. Do lagowirusów należą również: niepatogenny króliczy kaliciwirus RCV (Rabbit Calicivirus), o predylekcji do przewodu pokarmowego (15) oraz hepatotropowy, patogenny dla zajęcy Lepus europaeus i Lepus timidus wirus EBHS, zidentyfikowany w 1989 r. RHDV i EBHSV oprócz zbliżonej morfologii łączy występowanie krzyżowych reakcji antygenowych oraz struktura i organizacja genomu. Genom lagowirusów i kaliciwirusów z rodzajów Sapovirus i Nebovirus zawiera dwie, natomiast norowirusów i vesiwirusów trzy ramki odczytu (ORF). Obszerna ORF1 koduje jednolitą poliproteinę (257 kDa), z której w wyniku działania wirusowej proteazy powstają białka niestrukturalne i strukturalne białko kapsydu VP60 (60 kDa). ORF2 koduje mniejsze biał-ko strukturalne VP10. W kapsydzie występuje także subgenomowy RNA (2,2 kb), który również koduje białko VP60 oraz bierze udział w procesach transkrypcji i translacji (55). Pomimo dużego podobieństwa genetycznego RHDV i EBHSV (52-60% i 63-70% homologia sekwencji nukleotydów i aminokwasów w obrębie genu vp60) są to całkowicie odrębne patogeny, niezdolne do zakażenia krzyżowego królików i zajęcy, których nie można namnożyć in vitro w systemach hodowli komórkowych oraz w zarodkach kurzych (16,32,58).W diagnostyce wirusologicznej RHD stosuje się techniki mikroskopii elektronowej (EM/IEM) umożliwiają-ce bezpośrednią detekcję kubicznych cząstek o średnicy 27-40 nm, metody immunoenzymatyczne ELISA do wykrywania antygenu oraz odczyn hemaglutynacji do określenia właściwości hemaglutynacyjnych. Techniki molekularne, takie jak: amplifikacja wirusowego RNA metodą RT-PCR, real-time RT-PCR (RTq-PCR) oraz sekwencjonowanie wykorzystuje się do określenia typu wirusa oraz w badaniach filogenetycznych. Zakażenie doświadczalne podatnych królików jest metodą stosowaną do potwierdzenia rozpoznania oraz podczas produkcji szczepionek: do namnożenia wirusa i kontroli serii. Ważnym elementem diagnostyki RHD są metody serologiczne: odczyn zahamowania hemaglutynacji i test ELISA (OIE Manual 2016, rozdział 2.6.2). Niepatogenne kaliciwirusy królikówWczesne dowody mówiące o wysoce prawdopodobnym występowaniu bliskiego, niepatogennego przodka RHDV pochodzą z badań archiwalnych surowic króli-ków europejskich z połowy lat 70., w których wykryto swoiste przeciwciała (61) oraz z ...

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Emergence of Pathogenicity in Lagoviruses: Evolution from Pre-existing Nonpathogenic Strains or through a Species Jump?

Abstract: International audienceno abstrac

Cited by 33 publications

References 92 publications

Epidemiology of RHDV2 (Lagovirus europaeus/GI.2) in free-living wild European rabbits in Portugal

Epidemiology of RHDV2 (Lagovirus europaeus/GI.2) in free-living wild European rabbits in Portugal

Benign Rabbit Caliciviruses Exhibit Evolutionary Dynamics Similar to Those of Their Virulent Relatives

Diversity of RHD virus: epidemiological, diagnostic and immunological importance

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