Global Gene Expression Analysis of the Brainstem in EV71- and CVA16-Infected Gerbils

Sun, Yisheng; Yang, Zhangnv; Fang, Xu; Chen, Chen; Lu, Hang-Jing; Jiang, Jianmin; Zhang, Yanjun; Zhu, Han-Ping; Yao, Pingping

doi:10.3390/v12010046

Cited by 15 publications

(8 citation statements)

References 26 publications

(31 reference statements)

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“…Interestingly, inhibition of C5aR1 was reportedly shown to confer a considerable level of protection in brain disorders involving neuroinflammatory responses and blood brain barrier disruption (Jacob and Alexander 2014 ). Jiang et al ( 2019 ) reported complement overactivation in macrophages, which resulted in immunopathology with overexpression of caspase-1 and IL-1β levels in the serum, and subsequently, pyroptosis of these cells in a mouse model of MERS-CoV infection (Jiang et al 2019 ). Notwithstanding, treatment with anti-C5aR1 antibody effectively suppressed the expression of caspase-1 and IL-1β, to abrogate the immunopathology and pyroptosis of the macrophages, suggesting that C5a/C5aR1 signalling pathway constitutes a potential target for the treatment of SARS-CoV-2 infection (Jiang et al 2019 ).…”

Section: Neuroimmune Dysregulation By Sars-cov-2 Neuroinvasionmentioning

confidence: 99%

Neuropathophysiology of coronavirus disease 2019: neuroinflammation and blood brain barrier disruption are critical pathophysiological processes that contribute to the clinical symptoms of SARS-CoV-2 infection

Welcome

Mastorakis

2021

Inflammopharmacol

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Coronavirus disease 2019 (COVID-19) is caused by the novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) first discovered in Wuhan, Hubei province, China in December 2019. SARS-CoV-2 has infected several millions of people, resulting in a huge socioeconomic cost and over 2.5 million deaths worldwide. Though the pathogenesis of COVID-19 is not fully understood, data have consistently shown that SARS-CoV-2 mainly affects the respiratory and gastrointestinal tracts. Nevertheless, accumulating evidence has implicated the central nervous system in the pathogenesis of SARS-CoV-2 infection. Unfortunately, however, the mechanisms of SARS-CoV-2 induced impairment of the central nervous system are not completely known. Here, we review the literature on possible neuropathogenic mechanisms of SARS-CoV-2 induced cerebral damage. The results suggest that downregulation of angiotensin converting enzyme 2 (ACE2) with increased activity of the transmembrane protease serine 2 (TMPRSS2) and cathepsin L in SARS-CoV-2 neuroinvasion may result in upregulation of proinflammatory mediators and reactive species that trigger neuroinflammatory response and blood brain barrier disruption. Furthermore, dysregulation of hormone and neurotransmitter signalling may constitute a fundamental mechanism involved in the neuropathogenic sequelae of SARS-CoV-2 infection. The viral RNA or antigenic peptides also activate or interact with molecular signalling pathways mediated by pattern recognition receptors (e.g., toll-like receptors), nuclear factor kappa B, Janus kinase/signal transducer and activator of transcription, complement cascades, and cell suicide molecules. Potential molecular targets and therapeutics of SARS-CoV-2 induced neurologic damage are also discussed.

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Section: Neuroimmune Dysregulation By Sars-cov-2 Neuroinvasionmentioning

confidence: 99%

Neuropathophysiology of coronavirus disease 2019: neuroinflammation and blood brain barrier disruption are critical pathophysiological processes that contribute to the clinical symptoms of SARS-CoV-2 infection

Welcome

Mastorakis

2021

Inflammopharmacol

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“…The consensus epitope (peptide M) was identified and antiviral properties were established by blocking viral protein expression [ 99 ]. Zhang et al [ 100 ] also reported the potential role of scFvs targeted against viral spike protein to inhibit PEDV infectivity by the plaque reduction neutralization assay and in the prevention and treatment of PEDV infection by oral administration [ 100 ]. Recently a rapid, low-cost, reliable blocking ELISA (bELISA) was developed using phage display technology employing VHH library and biopanning of nanobodies against PEDV N protein [ 70 ].…”

Section: Antibody Selection Against Coronaviruses Using Phage Displaymentioning

confidence: 99%

Phage Display Technique as a Tool for Diagnosis and Antibody Selection for Coronaviruses

et al. 2021

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Phage display is one of the important and effective molecular biology techniques and has remained indispensable for research community since its discovery in the year 1985. As a large number of nucleotide fragments may be cloned into the phage genome, a phage library may harbour millions or sometimes billions of unique and distinctive displayed peptide ligands. The ligand–receptor interactions forming the basis of phage display have been well utilized in epitope mapping and antigen presentation on the surface of bacteriophages for screening novel vaccine candidates by using affinity selection-based strategy called biopanning. This versatile technique has been modified tremendously over last three decades, leading to generation of different platforms for combinatorial peptide display. The translation of new diagnostic tools thus developed has been used in situations arising due to pathogenic microbes, including bacteria and deadly viruses, such as Zika, Ebola, Hendra, Nipah, Hanta, MERS and SARS. In the current situation of pandemic of Coronavirus disease (COVID-19), a search for neutralizing antibodies is motivating the researchers to find therapeutic candidates against novel SARS-CoV-2. As phage display is an important technique for antibody selection, this review presents a concise summary of the very recent applications of phage display technique with a special reference to progress in diagnostics and therapeutics for coronavirus diseases. Hopefully, this technique can complement studies on host–pathogen interactions and assist novel strategies of drug discovery for coronaviruses.

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“…In this study, we observed severe histopathological injury, glial activation, and inflammatory infiltration after CVA6 infection. Increasing evidence suggests that abnormalities cytokines are associated with CNS complications caused by EVA71 and CVA16 infection [ 42 , 43 ]. After EVA71 infection, susceptible cells and nonspecific immune cells are stimulated first to produce cytokines such as TNF-α and IL-6.…”

Section: Discussionmentioning

confidence: 99%

A mouse-adapted CVA6 strain exhibits neurotropism and triggers systemic manifestations in a novel murine model

Liu

Sun

Tao

et al. 2022

Emerging Microbes & Infections

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CVA6 is one of Enteroviruses causing worldwide epidemics of HFMD with neurological and systemic complications. A suitable animal model is necessary for studying the pathogenesis of CVA6 and evaluating antiviral and vaccine efficacy. In this study, we generated a mouse-adapted CVA6 strain that successfully infected 10-day-old ICR mice via oral route. All infected mice were paralyzed and died within 11 dpi. Analysis of pathological changes and virus loads in fourteen tissues showed that CVA6 triggered systematic damage similar to i.p. inoculation route. Unlike i.p. route, we detected oral and gastrointestinal lesions with the presence of viral antigens. Both specific anti-CVA6 serum and inactivated vaccines successfully generated immune protection in mice. Meanwhile, we also established a successful infection of CVA6 via i.p. and i.m. route in 10-day-old mice. After infection, mice developed remarkably neurological signs and systemic manifestations such as emaciation, polypnea, quadriplegia, depilation and even death. Through i.p. inoculation, pathological examination showed brain and spinal cord damage caused by the virus infection with neuronal reduction, apoptosis, astrocyte activation, and recruitment of neutrophils and monocytes. Following neurological manifestation, the CVA6 infection became systemic, and high viral loads were detected in multiple organs along with morphological changes and inflammation. Moreover, analysis of spleen cells by FACS indicated that CVA6 led to immune system activation, which further contributed to systemic inflammation. Taken together, our novel murine model of CVA6 provides a useful tool for studying the pathogenesis and evaluating antiviral and vaccine efficacy.

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Global Gene Expression Analysis of the Brainstem in EV71- and CVA16-Infected Gerbils

Cited by 15 publications

References 26 publications

Neuropathophysiology of coronavirus disease 2019: neuroinflammation and blood brain barrier disruption are critical pathophysiological processes that contribute to the clinical symptoms of SARS-CoV-2 infection

Neuropathophysiology of coronavirus disease 2019: neuroinflammation and blood brain barrier disruption are critical pathophysiological processes that contribute to the clinical symptoms of SARS-CoV-2 infection

Phage Display Technique as a Tool for Diagnosis and Antibody Selection for Coronaviruses

A mouse-adapted CVA6 strain exhibits neurotropism and triggers systemic manifestations in a novel murine model

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