Electron and immunoelectron microscopy of rabbit haemorrhagic disease virus (RHDV)

Rabbit hemorrhagic disease was described in China in 1984 and can cause hemorrhagic necrosis of the liver within two or three days after infection. The etiological agent, rabbit hemorrhagic disease virus (RHDV), belongs to the Lagovirus genus in the Caliciviridae family. Compared to other calicivirus, such as rNV and SMSV, the structure of Lagovirus members is not well characterized. In this report, structures of two types of wild RHDV particles, the intact virion and the core-like particle (CLP), were reconstructed by cryo-electron microscopy at 11 Å and 17 Å, respectively. This is the first time the 3D structure of wild caliciviruses CLP has been provided, and the 3D structure of intact RHDV virion is the highest resolution structure in Lagovirus. Comparison of the intact virion and CLP structures clearly indicated that CLP was produced from the intact virion with the protrusion dissociated. In contrast with the crystal structures of recombinant Norovirus and San Miguel sea lion virus, the capsomers of RHDV virion exhibited unique structural features and assembly modes. Both P1 and P2 subdomains have interactions inside the AB capsomer, while only P2 subdomains have interaction inside CC capsomer. The pseudo atomic models of RHDV capsomers were constructed by homology modeling and density map fitting, and the rotation of RHDV VP60 P domain with respect to its S domain, compared with SMSV, was observed. Collectively, our cryo-electron microscopic studies of RHDV provide close insight into the structure of Lagovirus, which is important for functional analysis and better vaccine development in the future.

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“…1B) by negative staining. They might be the ferritin-like structures as previously reported (Valicek et al, 1990).…”

Section: Resultssupporting

confidence: 66%

“…It exhibits characteristic cup-shaped depressions on the surface with T = 3 icosahedral symmetry, which was revealed by negative staining electron microscopy (Valicek et al, 1990). As calicivirus, the shell of RHDV virion is mainly composed of major capsid protein VP60 (Clarke and Lambden, 1997).…”

Section: Introductionmentioning

confidence: 99%

Cryo-electron microscopy reconstructions of two types of wild rabbit hemorrhagic disease viruses characterized the structural features of Lagovirus

Tian

Zhai

et al. 2010

Protein Cell

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“…Its ultrastructure (~mid et al, 1989;Ohlinger et al, 1989;Vali~ek et al, 1990) and the presence and size of the dominant protein (61K) classes RHDV with caliciviruses. Such classification is supported by the finding that both RHDV and FCV contain dominant (capsid) proteins with very similar Mr values (60K to 61K and 62K to 64K), typical for caliciviruses (Carter et al, 1989;Capucci et al, 1990;Rodfik et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

“…Several reports (Liu et al, 1984;Gu et al, 1986; have described the production of inactivated vaccines with reliable protective effects, and haemagglutination and haemagglutination inhibition tests (HT and HIT respectively) were developed for the demonstration of the virus and specific antibodies (Liu et al, 1984;Pu et al, 1985;Duet al, 1986;Ohlinger et al, 1989). The earlier, rather controversial reports concerning the classification of RHDV (Liu et al, 1984;Du et al, 1986;Shen et al, 1986;Xu et al, 1988) were followed by several papers suggesting, on the basis of morphology, the size of the major structural proteins and density in CsC1, that RHDV is a calicivirus (Du et al, 1986;Deng et al, 1987 ;Ohlinger et al, 1989;~mid et al, 1989;Vali~ek et al, 1990). On the other hand, RHDV differs from known caliciviruses in several respects: its haemagglutinating activity and failure in all attempts to propagate it in vitro (Studdert, 1978;Cubitt, 1987;Carter et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Monoclonal antibodies to rabbit haemorrhagic disease virus and their use in the diagnosis of infection

Rodák

Granátová

Valíček

et al. 1990

Journal of General Virology

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Hybridomas producing monoclonal antibodies (MAbs) to rabbit haemorrhagic disease virus (RHDV) were prepared. Using Western blot (WB) analysis, the MAbs obtained were divided into two groups, one reacting with the major structural proteins of Mr 61K and 38K, and the other giving negative reactions. Both groups of MAbs, however, reacted specifically with RHDV in ELISA and by immunoperoxidase (IP) and immunofluorescence (IF) tests with infected ceils. As demonstrated by WB using RHDV-specific MAbs and a MAb to feline calicivirus (FCV) strain F9, the major structural (capsid) proteins of RHDV and FCV have very similar sizes (Mr 61K and 38K compared to 62K to 64K and 40K respectively). No cross-reactions of MAbs with proteins of the other virus were observed in WB analysis, ELISA, IP tests or IF. The high specificity and sensitivity of RHDV-specific MAbs make them suitable for the routine IP and IF diagnosis of RHDV in liver cells of rabbits dying after natural or experimental infections.

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“…RHDV and RCV-A1 represent different lineages within the genus Lagovirus of the family Caliciviridae (7)(8)(9)(10). RCV-A1 and RHDV share many genomic features, such as a polyadenylated single-stranded positive-sense RNA genome of around 7.5 kb organized into two overlapping open reading frames (ORFs) with a viral protein (VPg) covalently bound to the 5= end ( Fig.…”

mentioning

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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Electron and immunoelectron microscopy of rabbit haemorrhagic disease virus (RHDV)

Abstract: Rabbit haemorrhagic disease virus (RHDV) had a calicivirus-like structure and a diameter of 31.5-33.0 nm. Antigenic relationship between the investigated RHDV strain and the causal agent of RHD in China was demonstrated by immunoelectron microscopy.

Cited by 32 publications

References 8 publications

Cryo-electron microscopy reconstructions of two types of wild rabbit hemorrhagic disease viruses characterized the structural features of Lagovirus

Cryo-electron microscopy reconstructions of two types of wild rabbit hemorrhagic disease viruses characterized the structural features of Lagovirus

Monoclonal antibodies to rabbit haemorrhagic disease virus and their use in the diagnosis of infection

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

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