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Proteomic analysis of extremely severe hand, foot and mouth disease infected by enterovirus 71.

ABSTRACT: BACKGROUND: To clarify the molecular mechanisms that participate in the severe hand, foot and mouth disease (HFMD) infected by Enterovirus 71 and to detect any related protein biomarkers, we performed proteomic analysis of protein extracts from 5 extremely severe HFMD children and 5 healthy children. METHODS: The protein profiles of them were compared using two-dimensional electrophoresis. Differentially expressed proteins were identified using mass spectrometry. Functional classifications of these proteins were based on the PANTHER. The interaction network of the differentially expressed protein was generated with Pathway Studio. RESULTS: A total of 38 differentially expressed proteins were identified. Functional classifications of these proteins indicated a series of altered cellular processes as a consequence of the severe HFMD. These results provided not only new insights into the pathogenesis of severe HFMD, but also implications of potential therapeutic designs. CONCLUSIONS: Our results suggested the possible pathways that could be the potential targets for novel therapy: viral protection, complement system and peroxide elimination.

SUBMITTER: Deng L

PROVIDER: S-EPMC3765220 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Proteomic analysis of extremely severe hand, foot and mouth disease infected by enterovirus 71.

Deng Li L Jia Hong-Ling HL Liu Chao-Wu CW Xu Yu-Fen YF Mao Li-Jia LJ He Chun-Hui CH Yin Gen-Quan GQ Lin Jun-Hong JH Tao Jian-Ping JP Zhu Li L

BMC infectious diseases 20130820

<h4>Background</h4>To clarify the molecular mechanisms that participate in the severe hand, foot and mouth disease (HFMD) infected by Enterovirus 71 and to detect any related protein biomarkers, we performed proteomic analysis of protein extracts from 5 extremely severe HFMD children and 5 healthy children.<h4>Methods</h4>The protein profiles of them were compared using two-dimensional electrophoresis. Differentially expressed proteins were identified using mass spectrometry. Functional classifi ...[more]

PMID: 23961958

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Project description:Enterovirus 71 (EV71) and coxsackieviruses (CV) are the major causative agents of hand, foot and mouth disease (HFMD). There is not currently a vaccine available against HFMD, even though a newly developed formalin-inactivated EV71 (FI-EV71) vaccine has been tested in clinical trial and has shown efficacy against EV71. We have designed and genetically engineered a recombinant adenovirus Ad-EVVLP with the EV71 P1 and 3CD genes inserted into the E1/E3-deleted adenoviral genome. Ad-EVVLP were produced in HEK-293A cells. In addition to Ad-EVVLP particles, virus-like particles (VLPs) formed from the physical association of EV71 capsid proteins, VP0, VP1, and VP3 expressed from P1 gene products. They were digested by 3CD protease and confirmed to be produced by Ad-EVVLP-producing cells, as determined using transmission electron microscopy and western blotting. Mouse immunogenicity studies showed that Ad-EVVLP-immunized antisera neutralized the EV71 B4 and C2 genotypes. Activation of VLP-specific CD4+ and CD8+/IFN-γ T cells associated with Th1/Th2-balanced IFN-ɣ, IL-17, IL-4, and IL-13 was induced; in contrast, FI-EV71 induced only Th2-mediated neutralizing antibody against EV71 and low VLP-specific CD4+ and CD8+ T cell responses. The antiviral immunity against EV71 was clearly demonstrated in mice vaccinated with Ad-EVVLP in a hSCARB2 transgenic (hSCARB2-Tg) mouse challenge model. Ad-EVVLP-vaccinated mice were 100% protected and demonstrated reduced viral load in both the CNS and muscle tissues. Ad-EVVLP successfully induced anti-CVA16 immunities. Although antisera had no neutralizing activity against CVA16, the 3C-specific CD4+ and CD8+/IFN-γ T cells were identified, which could mediate protection against CVA16 challenge. FI-EV71 did not induce 3C-mediated immunity and had no efficacy against the CVA16 challenge. These results suggest that Ad-EVVLP can enhance neutralizing antibody and protective cellular immune responses to prevent EV71 infection and cellular immune responses against CV infection.

Dataset Information

Proteomic analysis of extremely severe hand, foot and mouth disease infected by enterovirus 71.

Publications

Proteomic analysis of extremely severe hand, foot and mouth disease infected by enterovirus 71.

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