Dissecting complicated viral spreading of enterovirus 71 using in situ bioorthogonal fluorescent labeling

Pan, Hong; Wang, Fangfang; He, Hongqing; Liu, Lanlan; He, Yaqing; Chen, Jinquan; Jiang, Puzi; Zhang, Renli; Ma, Yifan; Cai, Lintao

doi:10.1016/j.biomaterials.2018.07.061

Cited by 17 publications

(14 citation statements)

References 36 publications

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“…Reported mouse models either require innate deficient [10,11] or transgenic background [12,13]. In addition, mouse-adapted strain [12,[14][15][16][17] or a high dose of virus is needed to establish the virus infection model [11,[18][19][20]. Reported mouse models cannot recapitulate similar symptoms observed in humans such as pulmonary oedema [29], an important phenotype of EV71 infection in humans.…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, to establish EV71 mouse models, EV71 needs to be adapted as a mouse-adapted strain [12,[14][15][16][17] to get infectivity in the animals. Alternatively, a high dose of virus (as high as 10 6 -10 7 plaque-forming unit (PFU) per mouse) without adaptive mutations is needed to infect neonatal mice, transgenic mice or immunodeficient mice [11,[18][19][20].…”

Section: Introductionmentioning

confidence: 99%

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An infectious clone of enterovirus 71(EV71) that is capable of infecting neonatal immune competent mice without adaptive mutations

Zhang

Song

Zou

et al. 2020

Emerging Microbes & Infections

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Enterovirus 71 (EV71) is a major pathogen that causes hand, foot and mouth disease (HFMD), which is a life threatening disease in certain children. The pathogenesis of EV71-caused HFMD is poorly defined due to the lack of simple and robust animal models with severe phenotypes that recapitulate symptoms observed in humans. Here, we generated the infectious clone of a clinical isolate from a severe HFMD patient. Virus rescued from the cDNA clone was infectious in cell lines. When administrated intraperitoneally to neonatal ICR, BALB/c and C57 immune competent mice at a dosage of1.4 × 10 4 pfu per mouse, the virus caused weight loss, paralysis and death in the infected mice after 4-5 days of infection. In the infected mice, detectable viral replication was detected in various tissues such as heart, liver, brain, lung, kidney, small intestine, leg skeletal muscle and medulla oblongata. The histology of the infected mice included massive myolysis, glomerular atrophy, villous blunting in small intestine, widened alveolar septum, diminished alveolar spaces and lymphocytes infiltration into the lung. By using the UV-inactivated virus as a control, we elucidated that the virus first amplified in the leg skeletal muscle tissue and the muscle tissue served as a primary viral replication site. In summary, we generated a stable EV71 infectious clone that is capable of infecting neonatal immune competent mice without adaptive mutations and provide a simple, valuable animal model for the studies of EV71pathogenesis and therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An infectious clone of enterovirus 71(EV71) that is capable of infecting neonatal immune competent mice without adaptive mutations

Zhang

Song

Zou

et al. 2020

Emerging Microbes & Infections

View full text Add to dashboard Cite

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“…In recent years, bioorthogonal glycometabolic engineering was developed into a reliable technique for modulating cell-surface carbohydrates by the biosynthetic incorporation of unnatural sugars, which has emerged as a powerful tool to artificially label and modify target cells [ [17] , [18] , [19] ]. This novel technology employed the concept of artificial bioorthogonal targeting via chemical reaction between functional chemical reporters and their complementary groups in vivo [ 20 , 21 ]. Azide molecules conjugated monosaccharides are wildly used for glycometabolic labeling of target cells, due to its accessibility, small size, inertness and near absence in living system [ [22] , [23] , [24] ].…”

Section: Introductionmentioning

confidence: 99%

Click CAR-T cell engineering for robustly boosting cell immunotherapy in blood and subcutaneous xenograft tumor

Pan

Chen

et al. 2021

Bioactive Materials

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The adoptive transfer of chimeric antigen receptor-T (CAR-T) cells has shown remarkable clinical responses in hematologic malignancies. However, unsatisfactory curative results and side effects for tumor treatment are still unsolved problems. Herein we develop a click CAR-T cell engineering strategy via cell glycometabolic labeling for robustly boosting their antitumor effects and safety in vivo. Briefly, paired chemical groups (N 3 /BCN) are separately incorporated into CAR-T cell and tumor via nondestructive intrinsic glycometabolism of exogenous Ac 4 GalNAz and Ac 4 ManNBCN, serving as an artificial ligand-receptor. Functional groups anchored on cell surface strengthen the interaction of CAR-T cell and tumor via bioorthogonal click chemistry, further enhancing specific recognition, migration and selective antitumor effects of CAR-T cells. In vivo, click CAR-T cell completely removes lymphoma cells and minimizes off-target toxicity via selective and efficient bioorthogonal targeting in blood cancer. Surprisingly, compared to unlabeled cells, artificial bioorthogonal targeting significantly promotes the accumulation, deep penetration and homing of CAR-T cells into tumor tissues, ultimately improving its curative effect for solid tumor. Click CAR-T cell engineering robustly boosts selective recognition and antitumor capabilities of CAR T cells in vitro and in vivo, thereby holding a great potential for effective clinical cell immunotherapy with avoiding adverse events in patients.

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“…Moreover, chemical labeling may interfere with the interaction between viruses and cells. To date, only a few studies focused on dynamic visualization of the EV71 infection process have been reported [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Metabolic labeling of enterovirus 71 with quantum dots for the study of virus receptor usage

Luo

et al. 2021

J Nanobiotechnol

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Fluorescent labeling and dynamic tracking is a powerful tool for exploring virus infection mechanisms. However, for small-sized viruses, virus tracking studies are usually hindered by a lack of appropriate labeling methods that do not dampen virus yield or infectivity. Here, we report a universal strategy for labeling viruses with chemical dyes and Quantum dots (QDs). Enterovirus 71 (EV71) was produced in a cell line that stably expresses a mutant methionyl-tRNA synthetase (MetRS), which can charge azidonorleucine (ANL) to the methionine sites of viral proteins during translation. Then, the ANL-containing virus was easily labeled with DBCO-AF647 and DBCO-QDs. The labeled virus shows sufficient yield and no obvious decrease in infectivity and can be used for imaging the virus entry process. Using the labeled EV71, different functions of scavenger receptor class B, member 2 (SCARB2), and heparan sulfate (HS) in EV71 infection were comparatively studied. The cell entry process of a strong HS-binding EV71 strain was investigated by real-time dynamic visualization of EV71-QDs in living cells. Taken together, our study described a universal biocompatible virus labeling method, visualized the dynamic viral entry process, and reported details of the receptor usage of EV71. Graphic Abstract

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Dissecting complicated viral spreading of enterovirus 71 using in situ bioorthogonal fluorescent labeling

Cited by 17 publications

References 36 publications

An infectious clone of enterovirus 71(EV71) that is capable of infecting neonatal immune competent mice without adaptive mutations

An infectious clone of enterovirus 71(EV71) that is capable of infecting neonatal immune competent mice without adaptive mutations

Click CAR-T cell engineering for robustly boosting cell immunotherapy in blood and subcutaneous xenograft tumor

Metabolic labeling of enterovirus 71 with quantum dots for the study of virus receptor usage

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