Structural Basis of Glycan Recognition in Globally Predominant Human P[8] Rotavirus

Sun, Xiaoman; Dang, Lei; Li, Dandi; Qi, Jianxun; Wang, Mengxuan; Chai, Wengang; Zhang, Qing; Wang, Hong; Bai, Ruixia; Tan, Ming; Duan, Zhaojun

doi:10.1007/s12250-019-00164-7

Cited by 20 publications

(19 citation statements)

References 56 publications

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“…Purified mucin components (MUC1 and MUC4) are able to inhibit HIV-1 in vitro and prevent the transmission of HIV-1 from dendritic cells to CD4+ T cells [ 38 , 39 ]. Moreover, core 2 glycans of mucins bind to the rotavirus virion, thereby preventing the virus from recognizing the cellular receptors [ 40 ]. Furthermore, the presence of epithelial mucins, associated with a-2,6-linked sialic acid, on exosome-like vesicles from human tracheobronchial ciliated epithelium has been shown to contribute to their antiviral effect against the human influenza A virus, which is known to bind sialic acid.…”

Section: Resultsmentioning

confidence: 99%

Extracellular Vesicles in Human Preterm Colostrum Inhibit Infection by Human Cytomegalovirus In Vitro

et al. 2020

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Breast milk is a complex biofluid that nourishes infants, supports their growth and protects them from diseases. However, at the same time, breastfeeding is a transmission route for human cytomegalovirus (HCMV), with preterm infants being at a great risk of congenital disease. The discrepancy between high HCMV transmission rates and the few reported cases of infants with severe clinical illness is likely due to the protective effect of breast milk. The aim of this study was to investigate the anti-HCMV activity of human preterm colostrum and clarify the role of colostrum-derived extracellular vesicles (EVs). Preterm colostrum samples were collected and the EVs were purified and characterized. The in vitro anti-HCMV activity of both colostrum and EVs was tested against HCMV, and the viral replication step inhibited by colostrum-purified EVs was examined. We investigated the putative role EV surface proteins play in impairing HCMV infection using shaving experiments and proteomic analysis. The obtained results confirmed the antiviral action of colostrum against HCMV and demonstrated a remarkable antiviral activity of colostrum-derived EVs. Furthermore, we demonstrated that EVs impair the attachment of HCMV to cells, with EV surface proteins playing a role in mediating this action. These findings contribute to clarifying the mechanisms that underlie the protective role of human colostrum against HCMV infection.

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Section: Resultsmentioning

confidence: 99%

Extracellular Vesicles in Human Preterm Colostrum Inhibit Infection by Human Cytomegalovirus In Vitro

et al. 2020

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“…Rotavirus VP8*-HBGA interaction was measured as described previously by Huang et al [ 22 , 42 , 45 ]. Well-characterized saliva samples containing known HBGA types from our lab stock [ 46 ] were diluted 1000× and coated on microtiter plates.…”

Section: Methodsmentioning

confidence: 99%

A Nanoparticle-Based Trivalent Vaccine Targeting the Glycan Binding VP8* Domains of Rotaviruses

Xia

Huang

Jiang

et al. 2021

Viruses

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Rotavirus causes severe gastroenteritis in children. Although vaccines are implemented, rotavirus-related diarrhea still claims ~200,000 lives annually worldwide, mainly in low-income settings, pointing to a need for improved vaccine tactics. To meet such a public health need, a P24-VP8* nanoparticle displaying the glycan-binding VP8* domains, the major neutralizing antigens of rotavirus, was generated as a new type of rotavirus vaccine. We reported here our development of a P24-VP8* nanoparticle-based trivalent vaccine. First, we established a method to produce tag-free P24-VP8* nanoparticles presenting the VP8*s of P[8], P[4], and P[6] rotaviruses, respectively, which are the three predominantly circulating rotavirus P types globally. This approach consists of a chemical-based protein precipitation and an ion exchange purification, which may be scaled up for large vaccine production. All three P24-VP8* nanoparticle types self-assembled efficiently with authentic VP8*-glycan receptor binding function. After they were mixed as a trivalent vaccine, we showed that intramuscular immunization of the vaccine elicited high IgG titers specific to the three homologous VP8* types in mice. The resulted mouse sera strongly neutralized replication of all three rotavirus P types in cell culture. Thus, the trivalent P24-VP8* nanoparticles are a promising vaccine candidate for parenteral use against multiple P types of predominant rotaviruses.

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“…It occurs at approximately 0.8 to almost 5 g/L in human milk (Elwakiel et al, 2018;Galeotti et al, 2014;Musumeci, Simpore, D'Agata, Sotgiu, & Musumeci, 2006), generally in a decreasing pattern from colostrum to mature milk. Although interest into LNFP-I function has been fueled by its abundance in breast milk and its molecular structure being closely linked to human-microbial co-evolution (Urashima et al, 2012), only preliminary studies have been published to date, suggesting immunomodulatory, antiviral, bacteriostatic, and antiinfective activity of LNFP-I (Asakuma et al, 2010;Derya et al, 2020;Lin et al, 2017;Morrow et al, 2004;Morrow, Ruiz-Palacios, Jiang, & Newburg, 2005;Sun et al, 2020). More robust preclinical and clinical studies examining the biological effect of LNFP-I have thus far been largely precluded by the inability to produce this HMO on an industrial scale.…”

Section: Introductionmentioning

confidence: 99%

Genotoxicity and neonatal subchronic toxicity assessment of a novel mixture of the human‐identical milk oligosaccharides lacto‐N‐fucopentaose I and 2′‐fucosyllactose

Phipps

Lynch

Stannard

et al. 2020

J of Applied Toxicology

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Human milk oligosaccharides (HMOs) are a complex group of bioactive molecules largely observed in human breast milk but also occurring in limited amounts in other mammalian milks. Advances in biotechnology have enabled production of humanidentical milk oligosaccharides (HiMOs), structurally identical molecules to HMOs found naturally in human milk, intended for addition to infant formula to more closely replicate breast milk. Biosynthesis of a novel mixture of two major HMOs, lacto-N-fucopentaose I and 2 0-fucosyllactose (LNFP-I/2 0-FL), recently became possible. To support the safety of LNFP-I/2 0-FL for use in infant formula and other foods, it was subject to a safety assessment comprising a bacterial reverse mutation test, an in vitro mammalian cell micronucleus test, and a 90-day oral gavage study in neonatal rats. In the 90-day study (the first HiMO study to include the new endocrinesensitive endpoints described in the 2018 version of OECD Test Guideline 408), LNFP-I/2 0-FL was administered by oral gavage to neonatal rats once daily (from Day 7 of age) for 90 consecutive days, at doses up to 5000 mg/kg bw/day, followed by a 4-week recovery period. Concurrent reference controls received 5000 mg/kg bw/day of the approved infant formula ingredient oligofructose. LNFP-I/2 0-FL was nongenotoxic in vitro. The highest dose tested (5000 mg/kg bw/day) was established as the no-observed-adverse-effect level in the 90-day study, as there were no test article-related adverse effects on clinical observations, body weight, food consumption, clinical pathology, and organ weights nor any noteworthy macroscopic or microscopic findings. This supports the safety of LNFP-I/2 0-FL for its intended uses in food.

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Structural Basis of Glycan Recognition in Globally Predominant Human P[8] Rotavirus

Cited by 20 publications

References 56 publications

Extracellular Vesicles in Human Preterm Colostrum Inhibit Infection by Human Cytomegalovirus In Vitro

Extracellular Vesicles in Human Preterm Colostrum Inhibit Infection by Human Cytomegalovirus In Vitro

A Nanoparticle-Based Trivalent Vaccine Targeting the Glycan Binding VP8* Domains of Rotaviruses

Genotoxicity and neonatal subchronic toxicity assessment of a novel mixture of the human‐identical milk oligosaccharides lacto‐N‐fucopentaose I and 2′‐fucosyllactose

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