The SARS-CoV-2 spike (S) and the orthoreovirus p15 cause neuronal and glial fusion

Martínez-Mármol, Ramón; Giordano-Santini, Rosina; Kaulich, Eva; Cho, Ann-Na; Riyadh, M. Asrafuzzaman; Robinson, Emilija; Balistreri, Giuseppe; Meunier, Frédéric A.; Ke, Yazi D.; Ittner, Lars M.; Hilliard, Massimo A.

doi:10.1101/2021.09.01.458544

Cited by 3 publications

(3 citation statements)

References 47 publications

(47 reference statements)

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“…In this study, we generated hCOs using a previously published protocol [ 1 , 42 ] and demonstrated the potential of AAV for gene delivery. Across independently produced batches, hCOs showed reproducibility in all parameters measured including size, neuronal cell type markers, gene expression profile, and neuronal activity.…”

Section: Discussionmentioning

confidence: 99%

Efficient Gene Expression in Human Stem Cell Derived-Cortical Organoids Using Adeno Associated Virus

Cho

Bright

Morey

et al. 2022

Cells

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Cortical organoids are 3D structures derived either from human embryonic stem cells or human induced pluripotent stem cells with their use exploding in recent years due to their ability to better recapitulate the human brain in vivo in respect to organization; differentiation; and polarity. Adeno-associated viruses (AAVs) have emerged in recent years as the vectors of choice for CNS-targeted gene therapy. Here; we compare the use of AAVs as a mode of gene expression in cortical organoids; over traditional methods such as lipofectamine and electroporation and demonstrate its ease-of-use in generating quick disease models through expression of different variants of the central gene—TDP-43—implicated in amyotrophic lateral sclerosis and frontotemporal dementia.

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Section: Discussionmentioning

confidence: 99%

Efficient Gene Expression in Human Stem Cell Derived-Cortical Organoids Using Adeno Associated Virus

Cho

Bright

Morey

et al. 2022

Cells

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“…In addition, the invasion of SARS-CoV-2 into the brain might cause severe effects on brains, because only spike protein without replicating virus can cause syncytia which could cause apoptosis and cell death [54,55]. Moreover, human brain organoids and nervon cells expressing spike protein could lead to the formation of syncytia [56]. SARS-CoV-2-indcued fusion was correlated with the neurodegenerative disorders [50].…”

Section: Effects Of Sars-cov-2-mediated Syncytiamentioning

confidence: 99%

Long-term effects of SARS-CoV-2 infection on human brain and memory

Ding

Zhao

2023

Cell Death Discov.

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have caused several waves of outbreaks. From the ancestral strain to Omicron variant, SARS-CoV-2 has evolved with the high transmissibility and increased immune escape against vaccines. Because of the multiple basic amino acids in the S1-S2 junction of spike protein, the widespread distribution of angiotensin-converting enzyme 2 (ACE2) receptor in human body and the high transmissibility, SARS-CoV-2 can infect multiple organs and has led to over 0.7 billion infectious cases. Studies showed that SARS-CoV-2 infection can cause more than 10% patients with the Long-COVID syndrome, including pathological changes in brains. This review mainly provides the molecular foundations for understanding the mechanism of SARS-CoV-2 invading human brain and the molecular basis of SARS-CoV-2 infection interfering with human brain and memory, which are associated with the immune dysfunction, syncytia-induced cell death, the persistence of SARS-CoV-2 infection, microclots and biopsychosocial aspects. We also discuss the strategies for reducing the Long-COVID syndrome. Further studies and analysis of shared researches will allow for further clarity regarding the long-term health consequences.

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“…myocardial injury and thrombosis), and mortalities have been reported in relation to vaccination (28)(29)(30)(31). Although some side effects may stem from the delivery modalities, several studies have indicated that the spike protein alone causes adverse effects on host tissues, such as blood brain barrier disruption, neuron fusion, inflammation, and cell senescence (32)(33)(34)(35). Although it is difficult to detect the origin of side effects in vaccinated individuals, more investigation on the cellular effects of mRNA vaccines or the expressed protein antigen are warranted to create safer vaccines.…”

Section: Introductionmentioning

confidence: 99%

Are There Hidden Genes in DNA/RNA Vaccines?

et al. 2022

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Due to the fast global spreading of the Severe Acute Respiratory Syndrome Coronavirus – 2 (SARS-CoV-2), prevention and treatment options are direly needed in order to control infection-related morbidity, mortality, and economic losses. Although drug and inactivated and attenuated virus vaccine development can require significant amounts of time and resources, DNA and RNA vaccines offer a quick, simple, and cheap treatment alternative, even when produced on a large scale. The spike protein, which has been shown as the most antigenic SARS-CoV-2 protein, has been widely selected as the target of choice for DNA/RNA vaccines. Vaccination campaigns have reported high vaccination rates and protection, but numerous unintended effects, ranging from muscle pain to death, have led to concerns about the safety of RNA/DNA vaccines. In parallel to these studies, several open reading frames (ORFs) have been found to be overlapping SARS-CoV-2 accessory genes, two of which, ORF2b and ORF-Sh, overlap the spike protein sequence. Thus, the presence of these, and potentially other ORFs on SARS-CoV-2 DNA/RNA vaccines, could lead to the translation of undesired proteins during vaccination. Herein, we discuss the translation of overlapping genes in connection with DNA/RNA vaccines. Two mRNA vaccine spike protein sequences, which have been made publicly-available, were compared to the wild-type sequence in order to uncover possible differences in putative overlapping ORFs. Notably, the Moderna mRNA-1273 vaccine sequence is predicted to contain no frameshifted ORFs on the positive sense strand, which highlights the utility of codon optimization in DNA/RNA vaccine design to remove undesired overlapping ORFs. Since little information is available on ORF2b or ORF-Sh, we use structural bioinformatics techniques to investigate the structure-function relationship of these proteins. The presence of putative ORFs on DNA/RNA vaccine candidates implies that overlapping genes may contribute to the translation of smaller peptides, potentially leading to unintended clinical outcomes, and that the protein-coding potential of DNA/RNA vaccines should be rigorously examined prior to administration.

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The SARS-CoV-2 spike (S) and the orthoreovirus p15 cause neuronal and glial fusion

Cited by 3 publications

References 47 publications

Efficient Gene Expression in Human Stem Cell Derived-Cortical Organoids Using Adeno Associated Virus

Efficient Gene Expression in Human Stem Cell Derived-Cortical Organoids Using Adeno Associated Virus

Long-term effects of SARS-CoV-2 infection on human brain and memory

Are There Hidden Genes in DNA/RNA Vaccines?

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