Structural Evolution of the Emerging 2014-2015 GII.17 Noroviruses

Singh, B.K.; Koromyslova, A.D.; Hefele, Lisa; Gürth, Clara-Marie; Hansman, Grant S.

doi:10.1128/jvi.03119-15

Cited by 37 publications

(40 citation statements)

References 35 publications

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“…Our results indicated that the viruses produced in the immunocompromised host had no selective pressure to alter HBGA binding interactions but, rather, produced antigenic variants that could bind HBGAs. In contrast, in other noroviruses that cause acute infections, in particular the recently emerging GII.17 noroviruses, both the antigenicity and the HBGA pocket appeared to have been altered (42, 43). Interestingly, four of five residues (Asp374, Arg345, Thr344, Tyr444, and Gly443) that regularly interact with HBGAs were maintained in the chronic norovirus sequences.…”

Section: Discussionmentioning

confidence: 88%

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Human Norovirus Evolution in a Chronically Infected Host

Doerflinger

Weichert

Koromyslova

et al. 2017

mSphere

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The norovirus genogroup II genotype 4 (GII.4) variants have approximately 5% divergence in capsid amino acid identity and have dominated over the past decade. The precise reason(s) for the GII.4 emergence and persistence in the human population is still unknown, but some studies have suggested that chronically infected patients might generate novel variants that can cause new epidemics. We examined GII.4 noroviruses isolated from an immunocompromised patient with a long-term infection. Numerous norovirus capsid quasi-species were isolated during the 13-month study. The capsid quasi-species clustered into two genetic and antigenic types. However, the HBGA binding profiles were similar between the two antigenic clusters, indicating that the amino acid substitutions did not alter the HBGA binding interactions. The isolated sequences represented two new GII.4 variants, but similar sequences were not found in the database. These results indicated that chronically infected patients might not generate novel noroviruses that cause outbreaks.

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Section: Discussionmentioning

confidence: 88%

“…An antigen ELISA was used to determine the cross-reactivities of the norovirus VLPs with 11 different monoclonal antibodies raised against GII.4 strains and the patient’s and parents’ sera using an established method (42, 46). MaxiSorp 96-well microtiter plates were coated with 5 μg/ml VLPs.…”

Section: Methodsmentioning

confidence: 99%

Human Norovirus Evolution in a Chronically Infected Host

Doerflinger

Weichert

Koromyslova

et al. 2017

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“…Recently, a new GII.17 norovirus (NoV) variant caused significantly increased acute gastroenteritis outbreaks in China and other regions of Asia during 2014 and 2015 (42), which highlights the notion that a rare human NoV genotype has the potential to emerge as an epidemiologically important pathogen. The rare GII.17 NoVs also showed good binding in the saliva binding assay but did not bind to the oligosaccharides tested (42,43). This un- derscores the need for surveillance of the prevalence and evolution of P [19] RVs in humans and pigs.…”

Section: Discussionmentioning

confidence: 89%

Functional and Structural Characterization of P[19] Rotavirus VP8* Interaction with Histo-blood Group Antigens

Sun

Peng

et al. 2016

J Virol

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Rotaviruses (RVsR otaviruses (RVs) are the major causative agents of acute gastroenteritis in young children and animals worldwide (1). The RV genome contains 11 segments of double-stranded RNA encoding 12 proteins: six structural proteins (VP1, VP2, VP3, VP4, VP6, and VP7) and six nonstructural proteins (NSP1 to NSP6) (2). RVs are classified into 8 species (A to H) by the antigenicity of the VP6 protein (3). Group A rotavirus (RVA) is a major cause of human RV-associated gastroenteritis (4). RVA can be classified into various G and P types on the basis of glycoprotein VP7 and protease-sensitive VP4, respectively. To date, at least 27 G and 35 P genotypes have been reported (5). The fact that the segmented genome undergoes point mutations, reassortment, and gene rearrangements accounts for the large genetic diversity of RVs (1).VP4 can be cleaved by protease to yield N-terminal VP8* and C-terminal VP5* (6). VP8* includes the VP4 spike head and is reported to bind to cell surface glycans essential for cell invasion (7). The ability of a virus to invade host cells is crucial for its replication, host tropism, and pathogenicity. Notably, VP8* is the most variable domain. VP8* proteins of sialidase-sensitive RVs were reported to interact with sialic acids (Sia) (8); however, most animal RVs and almost all human RVs were sialidase insensitive (9). It was noted that many of the sialidase-insensitive RVA strains interact with Sia at subterminal sites of glycoprotein receptors (10). Recently, histo-blood group antigens (HBGAs) have been reported to be attachment factors for human RVs by interacting with VP8* (11,12). HBGAs are a group of carbohydrates present on the surfaces of red blood cells and mucosal epithelia and as free oligosaccharides in saliva, blood, and milk (13).Previous studies by oligosaccharide and saliva binding assays showed that P

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“…The VLPs were detected with serially diluted MAbs and then a secondary HRP-conjugated goat anti-mouse MAb (Sigma, Germany). Absorbance was measured at 490 nm (OD 490 ) and the binding cut-off was set to OD 490 = 0.15 as previously determined (31). All experiments were performed in triplicate.…”

Section: Methodsmentioning

confidence: 99%

Human Norovirus Neutralized by a Monoclonal Antibody Targeting the HBGA Pocket

Koromyslova

Morozov

Hefele

et al. 2018

Preprint

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22Temporal changes in the GII.4 human norovirus capsid sequences occasionally result 23 in the emergence of genetic variants capable of causing new epidemics. The GII.4 24 persistence is believed to be associated with the recognition of numerous histo-blood 25 group antigen (HBGA) types and antigenic drift. We found that one of the earliest 26 known GII.4 isolate (1974) and a more recent epidemic GII.4 variant (2012) had 27 varied norovirus-specific monoclonal antibody (MAb) reactivities, yet similar HBGA 28 binding profiles. To better understand the binding interaction of one MAb (10E9) that 29 had varied reactivities with these GII.4 variants, we determined the X-ray crystal 30 structure of the NSW-2012 GII.4 P domain 10E9 Fab complex. We showed that the 31 10E9 Fab interacted with conserved and variable residues, which could be associated 32 with antigenic drift. Interestingly, the 10E9 Fab binding pocket partially overlapped 33 the HBGA pocket and had direct competition for conserved HBGA binding residues 34 (i.e., Arg345 and Tyr444). Indeed, the 10E9 MAb blocked norovirus VLPs from 35 binding to several sources of HBGAs. Moreover, the 10E9 antibody completely 36 abolished virus replication in the human norovirus intestinal enteroid cell culture 37 system. Our new findings provide first direct evidence that competition for GII.4 38 HBGA binding residues and steric obstruction could lead to norovirus neutralization. 39On the other hand, the 10E9 MAb recognized residues flanking the HBGA pocket, 40 which are often substituted as the virus evolves. This mechanism of antigenic drift 41 likely influences herd immunity and impedes the possibility of acquiring broadly 42 reactive HBGA-blocking antibodies. 43 3 IMPORTANCE 44 45

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Structural Evolution of the Emerging 2014-2015 GII.17 Noroviruses

Cited by 37 publications

References 35 publications

Human Norovirus Evolution in a Chronically Infected Host

Human Norovirus Evolution in a Chronically Infected Host

Functional and Structural Characterization of P[19] Rotavirus VP8* Interaction with Histo-blood Group Antigens

Human Norovirus Neutralized by a Monoclonal Antibody Targeting the HBGA Pocket

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