Outbreak of Gastroenteritis Due to Sapovirus

Hansman, Grant S.; Saito, Hiroyuki; Shibata, Chihiro; Ishizuka, Shizuko; Oseto, Mitsuaki; Oka, Takahiro; Takeda, Naokazu

doi:10.1128/jcm.01854-06

Cited by 70 publications

(65 citation statements)

References 14 publications

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“…The full-length capsid genes, GI.1 (AY502016.1), GI.11, GII.1, GII.2, GII.4, GII.10, GII.12, and GII.17, were expressed in insect cells using the baculovirus expression system and stored in PBS [67,68].…”

Section: P Domain Productionmentioning

confidence: 99%

Nanobodies Targeting Norovirus Capsid Reveal Functional Epitopes and Potential Mechanisms of Neutralization

Koromyslova

Hansman

2018

Biophysical Journal

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Norovirus is the leading cause of gastroenteritis worldwide. Despite recent developments in norovirus propagation in cell culture, these viruses are still challenging to grow routinely. Moreover, little is known on how norovirus infects the host cells, except that histo-blood group antigens (HBGAs) are important binding factors for infection and cell entry. Antibodies that bind at the HBGA pocket and block attachment to HBGAs are believed to neutralize the virus. However, additional neutralization epitopes elsewhere on the capsid likely exist and impeding the intrinsic structural dynamics of the capsid could be equally important. In the current study, we investigated a panel of Nanobodies in order to probe functional epitopes that could trigger capsid rearrangement and/ or interfere with HBGA binding interactions. The precise binding sites of six Nanobodies (Nano-4, Nano-14, Nano-26, Nano-27, Nano-32, and Nano-42) were identified using X-ray crystallography. We showed that these Nanobodies bound on the top, side, and bottom of the norovirus protruding domain. The impact of Nanobody binding on norovirus capsid morphology was analyzed using electron microscopy and dynamic light scattering. We discovered that distinct Nanobody epitopes were associated with varied changes in particle structural integrity and assembly. Interestingly, certain Nanobody-induced capsid morphological changes lead to the capsid protein degradation and viral RNA exposure. Moreover, Nanobodies employed multiple inhibition mechanisms to prevent norovirus attachment to HBGAs, which included steric obstruction (Nano-14), allosteric interference (Nano-32), and violation of normal capsid morphology (Nano-26 and Nano-85). Finally, we showed that two Nanobodies (Nano-26 and Nano-85) not only compromised capsid integrity and inhibited VLPs attachment to HBGAs, but also recognized a broad panel of norovirus genotypes with high affinities. Consequently, Nano-26 and Nano-85 have a great potential to function as novel therapeutic agents against human noroviruses. PLOS Author summaryWe determined the binding sites of six novel human norovirus specific Nanobodies (Nano-4, Nano-14, Nano-26, Nano-27, Nano-32, and Nano-42) using X-ray crystallography. The unique Nanobody recognition epitopes were correlated with their potential neutralizing capacities. We showed that one Nanobody (Nano-26) bound numerous genogroup II genotypes and interacted with highly conserved capsid residues. Four Nanobodies (Nano-4, Nano-26, Nano-27, and Nano-42) bound to occluded regions on the intact particles and impaired normal capsid morphology and particle integrity. One Nanobody (Nano-14) bound contiguous to the HBGA pocket and interacted with several residues involved in binding HBGAs. We found that the Nanobodies delivered multiple inhibition mechanisms, which included steric obstruction, allosteric interference, and disruption of the capsid stability. Our data suggested that the HBGA pocket might not be an ideal target for drug development, since the surrounding regio...

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Section: P Domain Productionmentioning

confidence: 99%

Nanobodies Targeting Norovirus Capsid Reveal Functional Epitopes and Potential Mechanisms of Neutralization

Koromyslova

Hansman

2018

Biophysical Journal

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“…To the Editor: Sapovirus is an etiologic agent of human gastroenteritis. Although many of the previously reported cases were of mild, sporadic infections in young children (1-3), several recent sapovirus-associated gastroenteritis outbreaks have affected adults, which suggests that the virus's virulence, prevalence, or both, may be increasing (4)(5)(6). In this study, we describe a sapovirus-associated outbreak of gastroenteritis that occurred during May 4-8, 2007, and involved college students in northern Taiwan.…”

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confidence: 97%

Acute Gastroenteritis Caused by GI/2 Sapovirus, Taiwan, 2007

Wu¹,

Oka

Takeda

et al. 2007

Emerg. Infect. Dis.

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“…They are the causative agents of AGE in only a minority of cases of sporadic gastroenteritis in children. However, the incidence of sapovirusassociated gastroenteritis in adults is steadily increasing, suggesting a rise in virulence and prevalence [29,30]. In general, the severity of sapovirus gastroenteritis is milder than that of norovirus, and mortality is rare.…”

Section: Sapovirusmentioning

confidence: 99%

Diagnosis of viral gastroenteritis: limits and potential of currently available procedures

Sidoti

Rittá

Costa

et al. 2015

J Infect Dev Ctries

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The diagnostic approaches to viral gastroenteritis have evolved substantially over the past decades because of the advances in detection methods, the emergence of new pathogens, and the increase in diarrhea hospitalizations attributed to viruses, especially in young children in non-industrialized countries. Overall, these factors have lead to a relevant improvement of types and operating characteristics of diagnostic methods (including sensitivity and specificity), as well as turnaround time. In this review, clinical and laboratory approaches to the diagnosis of viruses causing gastroenteritis are presented; in particular, specimen collection and detection methods are reviewed and discussed, taking into account performance and limitations.

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Outbreak of Gastroenteritis Due to Sapovirus

Cited by 70 publications

References 14 publications

Nanobodies Targeting Norovirus Capsid Reveal Functional Epitopes and Potential Mechanisms of Neutralization

Nanobodies Targeting Norovirus Capsid Reveal Functional Epitopes and Potential Mechanisms of Neutralization

Acute Gastroenteritis Caused by GI/2 Sapovirus, Taiwan, 2007

Diagnosis of viral gastroenteritis: limits and potential of currently available procedures

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