Crystal structure of a nematode-infecting virus

Guo, Yusong R.; Hryc, Corey F.; Jakana, Joanita; Jiang, Hongbing; Wang, David; Chiu, Wah; Zhong, Weiwei; Tao, Yizhi Jane

doi:10.1073/pnas.1407122111

Cited by 32 publications

(48 citation statements)

References 41 publications

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“…The crystal structure of the Orsay capsid shows that the C-terminus of the Orsay CP is tucked underneath of a tightly bound trimeric spike [23] (S8 Fig). Therefore, for a trimeric fiber to form, the polypeptide sequence would have to go around the timeric spike from outside, spanning a distance of at least 60-Å in order to reach the 3-fold axis.…”

Section: Discussionmentioning

confidence: 99%

Structure of a pentameric virion-associated fiber with a potential role in Orsay virus entry to host cells

Fan¹,

Guo²,

Wang³

et al. 2017

PLoS Pathog

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Despite the wide use of Caenorhabditis elegans as a model organism, the first virus naturally infecting this organism was not discovered until six years ago. The Orsay virus and its related nematode viruses have a positive-sense RNA genome, encoding three proteins: CP, RdRP, and a novel δ protein that shares no homology with any other proteins. δ can be expressed either as a free δ or a CP-δ fusion protein by ribosomal frameshift, but the structure and function of both δ and CP-δ remain unknown. Using a combination of electron microscopy, X-ray crystallography, computational and biophysical analyses, here we show that the Orsay δ protein forms a ~420-Å long, pentameric fiber with an N-terminal α-helical bundle, a β-stranded filament in the middle, and a C-terminal head domain. The pentameric nature of the δ fiber has been independently confirmed by both mass spectrometry and analytical ultracentrifugation. Recombinant Orsay capsid containing CP-δ shows protruding long fibers with globular heads at the distal end. Mutant viruses with disrupted CP-δ fibers were generated by organism-based reverse genetics. These viruses were found to be either non-viable or with poor infectivity according to phenotypic and qRT-PCR analyses. Furthermore, addition of purified δ proteins to worm culture greatly reduced Orsay infectivity in a sequence-specific manner. Based on the structure resemblance between the Orsay CP-δ fiber and the fibers from reovirus and adenovirus, we propose that CP-δ functions as a cell attachment protein to mediate Orsay entry into worm intestine cells.

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Section: Discussionmentioning

confidence: 99%

Structure of a pentameric virion-associated fiber with a potential role in Orsay virus entry to host cells

Fan¹,

Guo²,

Wang³

et al. 2017

PLoS Pathog

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“…Structural features around the 3-fold axis are diverse in Nodaviridae-like and Tombusviridae-like viruses. In MCTV, grouper nervous necrosis virus (GNNV) (19), and Orsay virus (20), three N-arms form a trident structure as described above (18-20) ( Fig. 7E, Fig.…”

Section: Resultsmentioning

confidence: 93%

Cryo-electron Microscopy Structures of Novel Viruses from Mud Crab Scylla paramamosain with Multiple Infections

Gao

Liu

Huang

et al. 2019

J Virol

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Viruses associated with sleeping disease (SD) in crabs cause great economic losses to aquaculture, and no effective measures are available for their prevention. In this study, to help develop novel antiviral strategies, single-particle cryoelectron microscopy was applied to investigate viruses associated with SD. The results not only revealed the structure of mud crab dicistrovirus (MCDV) but also identified a novel mud crab tombus-like virus (MCTV) not previously detected using molecular biology methods. The structure of MCDV at a 3.5-Å resolution reveals three major capsid proteins (VP1 to VP3) organized into a pseudo-Tϭ3 icosahedral capsid, and affirms the existence of VP4. Unusually, MCDV VP3 contains a long C-terminal region and forms a novel protrusion that has not been observed in other dicistrovirus. Our results also reveal that MCDV can release its genome via conformation changes of the protrusions when viral mixtures are heated. The structure of MCTV at a 3.3-Å resolution reveals a Tϭ 3 icosahedral capsid with common features of both tombusviruses and nodaviruses. Furthermore, MCTV has a novel hydrophobic tunnel beneath the 5-fold vertex and 30 dimeric protrusions composed of the P-domains of the capsid protein at the 2-fold axes that are exposed on the virion surface. The structural features of MCTV are consistent with a novel type of virus. IMPORTANCE Pathogen identification is vital for unknown infectious outbreaks, especially for dual or multiple infections. Sleeping disease (SD) in crabs causes great economic losses to aquaculture worldwide. Here we report the discovery and identification of a novel virus in mud crabs with multiple infections that was not previously detected by molecular, immune, or traditional electron microscopy (EM) methods. High-resolution structures of pathogenic viruses are essential for a molecular understanding and developing new disease prevention methods. The three-dimensional (3D) structure of the mud crab tombus-like virus (MCTV) and mud crab dicistrovirus (MCDV) determined in this study could assist the development of antiviral inhibitors. The identification of a novel virus in multiple infections previously missed using other methods demonstrates the usefulness of this strategy for investigating multiple infectious outbreaks, even in humans and other animals.

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“…Several unique characteristics of these nematode viruses have suggested that they represent a new and distinct group of nodavirus-like pathogens. For one, the OV capsid structure is more similar to that of piscine betanodaviruses than that of alphanodaviruses (36,37). Furthermore, although these nematode viruses encode an RdRP and capsid protein (CP) on RNA1 and RNA2 segments, respectively, they also encode an additional ORF downstream of the CP on RNA2 called ␦ that is unrelated to any known protein, and these viruses also do not encode the subgenomic (RNA3) segment typically found in nodaviruses (13,38).…”

Section: Nonnatural Virus Models (I) Flock House Virusmentioning

confidence: 99%

Caenorhabditis elegans as an Emerging Model for Virus-Host Interactions

Gammon

2017

J Virol

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Since 1999, Caenorhabditis elegans has been extensively used to study microbe-host interactions due to its simple culture, genetic tractability, and susceptibility to numerous bacterial and fungal pathogens. In contrast, virus studies have been hampered by a lack of convenient virus infection models in nematodes. The recent discovery of a natural viral pathogen of C. elegans and development of diverse artificial infection models are providing new opportunities to explore virushost interplay in this powerful model organism.KEYWORDS Caenorhabditis elegans, Flock House virus, innate immunity, Orsay virus, RNA interference, virus-host interactions, vesicular stomatitis virus I n the past 40 years, the free-living nematode Caenorhabditis elegans has been used in diverse fields such as neurobiology, RNA interference (RNAi), and pathogen-host interactions. As a model, C. elegans offers many advantages, including genetic tractability, small size, and inexpensive culture. Its sexually dimorphic nature and short reproductive cycle make genetic crosses and rearing large numbers of animals simple. As C. elegans naturally feeds on bacteria (1), one can often initiate intestinal infection by using the microbe of interest as a food source. Furthermore, the transparent body of C. elegans permits visualization of fluorescently tagged pathogens and tissue pathologies. Well-defined techniques for genetically modifying the laboratory strain (N2) make identifying nematode factors influencing pathogen susceptibilities relatively straightforward (2, 3). RNAi is also easily performed by feeding nematodes bacteria expressing double-stranded RNAs (dsRNAs) targeting the gene of interest. This "feeding" RNAi response spreads to most tissues and can be inherited, allowing inhibition of gene expression in adults and progeny.Although lacking the classic adaptive immunity found in vertebrates that relies on specialized immune cells, C. elegans employs a variety of innate and nonclassic adaptive immune responses that are shared with other metazoans (i.e., antiviral RNAi) (4, 5). An estimated 38% of the ϳ20,250 protein-encoding genes in C. elegans have human orthologs (6), and several antimicrobial pathways found in mammals are also found in worms (4,5,(7)(8)(9). Therefore, C. elegans can be used to explore conserved immunological mechanisms.Since the establishment of a Pseudomonas aeruginosa infection model in 1999 (10, 11), dozens of bacterial and fungal pathogens (including several that infect humans) have been shown to cause disease in C. elegans (reviewed in [1,9]). Studies of these predominantly extracellular pathogens have largely shaped our understanding of C. elegans immunity. However, with the recent discovery of natural intracellular pathogens of C. elegans (12, 13) and the development of nonnatural virus infection models (14-18), this is beginning to change.Here virus-C. elegans interaction models (Table 1) are discussed in terms of their features, advantages/disadvantages, and contributions to our understanding of C. elegan...

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Crystal structure of a nematode-infecting virus

Cited by 32 publications

References 41 publications

Structure of a pentameric virion-associated fiber with a potential role in Orsay virus entry to host cells

Structure of a pentameric virion-associated fiber with a potential role in Orsay virus entry to host cells

Cryo-electron Microscopy Structures of Novel Viruses from Mud Crab Scylla paramamosain with Multiple Infections

Caenorhabditis elegans as an Emerging Model for Virus-Host Interactions

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