EV71 virus-like particles produced by co-expression of capsid proteins in yeast cells elicit humoral protective response against EV71 lethal challenge

Wang, Xiaowen; Xiao, Xilong; Zhao, Miao; Liu, Wei; Lin, Peng; Sun, Xin; Cen, Shan; Yang, Burton B.; Huang, Yuming; Wang, Sheng; Zeng, Yi

doi:10.1186/s13104-015-1780-x

Cited by 15 publications

(8 citation statements)

References 50 publications

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“…EV71 belongs to the Picornaviridae family, and their genes encode 60 copies of the VP1, VP2, VP3, and VP4 proteins to form viral icosahedral capsids. 9 VP1 is a structural protein and an important target for the development of antiviral drugs. 10 It plays a key role in the release of RNA when the virus is attached to a host cell.…”

Section: ■ Introductionmentioning

confidence: 99%

Design, Synthesis, and Evaluation of Novel Enterovirus 71 Inhibitors as Therapeutic Drug Leads for the Treatment of Human Hand, Foot, and Mouth Disease

Zhang

Wang

et al. 2020

J. Med. Chem.

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Human hand, foot, and mouth disease (HFMD) is a serious public health threat with high infection rates in children and infants who reside in Asia and the Pacific regions, and no effective drugs are currently available. Enterovirus 71 (EV71) and coxsackievirus A16 are the major etiological pathogens. Based on an essential hydrophobic pocket on the viral capsid protein VP1, we designed and synthesized a series of small molecular weight compounds as inhibitors of EV71. A potential drug candidate named NLD-22 exhibited excellent antiviral activity (with an EC50 of 5.056 nM and a 100% protection rate for mice at a dose of 20 mg/kg) and low toxicity. NLD-22 had a favorable pharmacokinetic profile. High-resolution cryo-electron microscopy structural analysis confirmed NLD-22 bound to the hydrophobic pocket in VP1 to block viral infection. In general, NLD-22 was indicated to be a promising potential drug candidate for the treatment of HFMD.

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Section: ■ Introductionmentioning

confidence: 99%

Design, Synthesis, and Evaluation of Novel Enterovirus 71 Inhibitors as Therapeutic Drug Leads for the Treatment of Human Hand, Foot, and Mouth Disease

Zhang

Wang

et al. 2020

J. Med. Chem.

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“…These particles are suitable for mucosal immunization due to their resistance to proteolytic degradation and compatibility with mucosal environment [129]. Yeast VLP scaffolds have been used to display immunogenic antigens from pathogens such as porcine circovirus [130], rabbit hemorrhagic disease virus [131], coxsackievirus A6 [132], hepatitis B virus [133], Zika virus [128], chikungunya virus [134], dengue virus [135], enterovirus [127,136].…”

Section: Biotechnological Exploitation Of Yeast To Create Vaccine mentioning

confidence: 99%

Sneaking Out for Happy Hour: Yeast-Based Approaches to Explore and Modulate Immune Response and Immune Evasion

Angrand

Quillévéré

Daskalogianni

et al. 2019

Genes

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Many pathogens (virus, bacteria, fungi, or parasites) have developed a wide variety of mechanisms to evade their host immune system. The budding yeast Saccharomyces cerevisiae has successfully been used to decipher some of these immune evasion strategies. This includes the cis-acting mechanism that limits the expression of the oncogenic Epstein–Barr virus (EBV)-encoded EBNA1 and thus of antigenic peptides derived from this essential but highly antigenic viral protein. Studies based on budding yeast have also revealed the molecular bases of epigenetic switching or recombination underlying the silencing of all except one members of extended families of genes that encode closely related and highly antigenic surface proteins. This mechanism is exploited by several parasites (that include pathogens such as Plasmodium, Trypanosoma, Candida, or Pneumocystis) to alternate their surface antigens, thereby evading the immune system. Yeast can itself be a pathogen, and pathogenic fungi such as Candida albicans, which is phylogenetically very close to S. cerevisiae, have developed stealthiness strategies that include changes in their cell wall composition, or epitope-masking, to control production or exposure of highly antigenic but essential polysaccharides in their cell wall. Finally, due to the high antigenicity of its cell wall, yeast has been opportunistically exploited to create adjuvants and vectors for vaccination.

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“…There are two types of viruses, in terms of virus structure: nonenveloped and enveloped. Generally, enveloped viruses are released through budding, while nonenveloped viruses exit via cell lysis after intracellular assembly (Welsch et al 2007;Kushnir et al 2012). It is unlikely that mammalian-like virus budding is possible in yeasts: unlike mammalian cells, the outer cell membrane of yeast is covered by a wall composed of mannoprotein, a fibrous b1,3-glucan, b1,6-glucan and chitin (Lipke and Ovalle 1998).…”

Section: Enveloped Vlps Produced By Buddingmentioning

confidence: 99%

“…VP0, VP1 and VP3 make up its capsids and are each processed from P1 polypeptide by the 3CD viral protease (Li et al 2013;Zhao et al 2013a). Multilayered VLPs of coxsackievirus A16 and enterovirus 71 have been produced in both S. cerevisiae and P. pastoris by intracellular expression strategies (Li et al 2013;Zhao et al 2013a;Zhang et al 2015;Wang et al 2016). There are two different types of expression strategies for expression plasmids.…”

Section: Multilayered Vlps Produced In Yeastsmentioning

confidence: 99%

Yeast as an expression system for producing virus-like particles: what factors do we need to consider?

Kim

2016

Lett Appl Microbiol

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The development of various types of virus-like particles (VLPs) has accelerated over the past two decades as the importance of VLPs for generating nextgeneration vaccines has been appreciated. Yeast has advantages such as scalable fermentation, low risk of contamination by adventitious agents, low production costs and the ability to produce VLPs with reliable qualities. It is generally recognized that yeast is suitable for producing VLPs that have simple structures and are produced intracellularly. However, recently there has been much effort to extend its applicability, and there is now evidence that it can be used as an expression platform for the productions of VLPs not only of nonenveloped viruses but also of enveloped viruses. Moreover, evidences indicated that yeast allows secretory VLP productions. Meanwhile, it has become evident that the quality and quantity of yeast-derived VLPs are influenced by the choice of plasmid and promoter, the ratio of the structural proteins produced. Here, we review the characteristics of the yeast expression system in terms of the production of VLP and compare it with other expression systems. We also consider strategies for VLP production in yeast and factors that need to be taken into account.

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EV71 virus-like particles produced by co-expression of capsid proteins in yeast cells elicit humoral protective response against EV71 lethal challenge

Cited by 15 publications

References 50 publications

Design, Synthesis, and Evaluation of Novel Enterovirus 71 Inhibitors as Therapeutic Drug Leads for the Treatment of Human Hand, Foot, and Mouth Disease

Design, Synthesis, and Evaluation of Novel Enterovirus 71 Inhibitors as Therapeutic Drug Leads for the Treatment of Human Hand, Foot, and Mouth Disease

Sneaking Out for Happy Hour: Yeast-Based Approaches to Explore and Modulate Immune Response and Immune Evasion

Yeast as an expression system for producing virus-like particles: what factors do we need to consider?

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