Hand-Foot-and-Mouth Disease-Associated Enterovirus and the Development of Multivalent HFMD Vaccines

Zhang, Xinglong; Zhang, Yifan; Li, Heng; Liu, Longding

doi:10.3390/ijms24010169

Cited by 40 publications

(20 citation statements)

References 92 publications

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“…Focusing on cellular mechanisms exploited by viruses presents distinct advantages in treating emerging viruses, as opposed to directly targeting viral proteins. Cellular targets exhibit greater resistance to mutational changes over time, ensuring stability and suitability for development of therapeutics 47 . This stability reduces the chances of mutational escape and minimizes the risk of drug resistance, especially during the emergence of new viruses 48 .…”

Section: Discussionmentioning

confidence: 99%

Hyperglycemia facilitates EV71 replication: Insights into miR-206-mediated regulation of G3BP2 promoting EV71 IRES activity

Lai,

Chow,

Lin

et al. 2024

Theranostics

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Background: Neurotropic virus infections actively manipulate host cell metabolism to enhance virus neurovirulence. Although hyperglycemia is common during severe infections, its specific role remains unclear. This study investigates the impact of hyperglycemia on the neurovirulence of enterovirus 71 (EV71), a neurovirulent virus relying on internal ribosome entry site (IRES)-mediated translation for replication. Methods: Utilizing hSCARB2-transgenic mice, we explore the effects of hyperglycemia in EV71 infection and elucidate the underlying mechanisms. Results: Remarkably, administering insulin alone to reduce hyperglycemia in hSCARB2-transgenic mice results in a decrease in brainstem encephalitis and viral load. Conversely, induced hyperglycemia exacerbates neuropathogenesis, highlighting the pivotal role of hyperglycemia in neurovirulence. Notably, miR-206 emerges as a crucial mediator induced by viral infection, with its expression further heightened by hyperglycemia and concurrently repressed by insulin. The use of antagomiR-206 effectively mitigates EV71-induced brainstem encephalitis and reduces viral load. Mechanistically, miR-206 facilitates IRES-driven virus replication by repressing the stress granule protein G3BP2. Conclusions: Novel therapeutic approaches against severe EV71 infections involve managing hyperglycemia and targeting the miR-206-stress granule pathway to modulate virus IRES activity.

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Section: Discussionmentioning

confidence: 99%

Hyperglycemia facilitates EV71 replication: Insights into miR-206-mediated regulation of G3BP2 promoting EV71 IRES activity

Lai,

Chow,

Lin

et al. 2024

Theranostics

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“…The prevalence spectrum of HFMD virus changed significantly after EVA71 vaccination. 29 According to relevant epidemiological findings, the number of cases of morbidity, severe illnesses, and deaths associated with EVA71 decreased significantly in China, whereas the proportion of severe HFMD cases caused by non-EVA71 enteroviruses increased from 2017 to 2019. 30 The prevalence of CVA6 and CVA16 have significantly exceeded EVA71, which implying that an investigation on prevalence of non-EVA71 enteroviruses is imperative.…”

Section: Discussionmentioning

confidence: 99%

“…Since December 2015, the China Food and Drug Administration approved the EVA71 vaccine, and the vaccination for HFMD had been carried out in a timely manner in Henan. The prevalence spectrum of HFMD virus changed significantly after EVA71 vaccination 29 . According to relevant epidemiological findings, the number of cases of morbidity, severe illnesses, and deaths associated with EVA71 decreased significantly in China, whereas the proportion of severe HFMD cases caused by non‐EVA71 enteroviruses increased from 2017 to 2019 30 .…”

Section: Discussionmentioning

confidence: 99%

Emerging concerns of atypical hand foot and mouth disease caused by recombinant Coxsackievirus A6 variants in Henan, China

Chen,

et al. 2023

Journal of Medical Virology

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An increasing number of studies have reported that atypical hand, foot, and mouth disease (HFMD) is becoming a new concern for children's health. At present, there is no official definition for atypical HFMD, but some studies have defined that it occurs at anatomic sites not listed in the definition of HFMD issued by the World Health Organization. Several pathogens have been reported to cause atypical HFMD, such as Coxsackievirus (CV)A6. As one of the most prevalent enteroviruses in the world, CVA6 seems to affect a wider range of children and causes more severe and prolonged illness than other enteroviruses. The early lesions of atypical HFMD are very similar to the clinical presentations of other diseases, such as eczema, which poses a challenge for clinicians aiming to identify and diagnose HFMD in a timely manner. Here, we report on six atypical HFMD patients caused by recombinant CVA6 variants, and the atypical manifestations include eczema coxsackium, large herpes, rice‐like red papules and herpes, purpuric rash, and onychomadesis, as well as and large red herpes on scalp, perianal, testicles, shoulders and neck, and other atypical eruption sites, hoping to draw the attention of other pediatricians. This study will provide scientific guidance for timely diagnosis of HFMD to prevent serious complications.

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“…Nail changes, such as shedding, may follow HFMD after a latency period. However, there are uncommon neurological or cardiac complications, such as meningitis and acute flaccid paralysis, that can be fatal [19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Identification of a Conserved, Linear Epitope on VP3 of Enterovirus A Species Recognized by a Broad-Spectrum Monoclonal Antibody

Lie

Zhang

Jin

et al. 2023

Viruses

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Outbreaks of hand, foot and mouth disease (HFMD) have occurred frequently in the Asian-Pacific region over the last two decades, caused mainly by the serotypes in Enterovirus A species. High-quality monoclonal antibodies (mAbs) are needed to improve the accuracy and efficiency of the diagnosis of enteroviruses associated HFMD. In this study, a mAb 1A11 was generated using full particles of CV-A5 as an immunogen. In indirect immunofluorescence and Western blotting assays, 1A11 bound to the viral proteins of CV-A2, CV-A4, CV-A5, CV-A6, CV-A10, CV-A16, and EV-A71 of the Enterovirus A and targeted VP3. It has no cross-reactivity to strains of Enterovirus B and C. By mapping with over-lapped and truncated peptides, a minimal and linear epitope 23PILPGF28 was identified, located at the N-terminus of the VP3. A BLAST sequence search of the epitope in the NCBI genus Enterovirus (taxid: 12059) protein database indicates that the epitope sequence is highly conserved among the Enterovirus A species, but not among the other enterovirus species, first reported by us. By mutagenesis analysis, critical residues for 1A11 binding were identified for most serotypes of Enterovirus A. It may be useful for the development of a cost-effective and pan-Enterovirus A antigen detection for surveillance, early diagnosis and differentiation of infections caused by the Enterovirus A species.

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Hand-Foot-and-Mouth Disease-Associated Enterovirus and the Development of Multivalent HFMD Vaccines

Cited by 40 publications

References 92 publications

Hyperglycemia facilitates EV71 replication: Insights into miR-206-mediated regulation of G3BP2 promoting EV71 IRES activity

Hyperglycemia facilitates EV71 replication: Insights into miR-206-mediated regulation of G3BP2 promoting EV71 IRES activity

Emerging concerns of atypical hand foot and mouth disease caused by recombinant Coxsackievirus A6 variants in Henan, China

Identification of a Conserved, Linear Epitope on VP3 of Enterovirus A Species Recognized by a Broad-Spectrum Monoclonal Antibody

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