SARS-CoV-2 Invades the Central Nervous System via the Olfactory Route in Rhesus Monkeys
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA704283 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13769600_1.fastq.gz | Fastqsanger.gz | |||
| SRR13769600_2.fastq.gz | Fastqsanger.gz | |||
| SRR13769601_1.fastq.gz | Fastqsanger.gz | |||
| SRR13769601_2.fastq.gz | Fastqsanger.gz | |||
| SRR13769602_1.fastq.gz | Fastqsanger.gz |
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Project description:Zika virus (ZIKV) is associated with severe neuropathology in neonates as well as Guillain-Barré syndrome and other neurologic disorders in adults. Prolonged viral shedding has been reported in semen, suggesting the presence of anatomic viral reservoirs. Here we show that ZIKV can persist in cerebrospinal fluid (CSF) and lymph nodes (LN) of infected rhesus monkeys for weeks after virus has been cleared from peripheral blood, urine, and mucosal secretions. ZIKV-specific neutralizing antibodies correlated with rapid clearance of virus in peripheral blood but remained undetectable in CSF for the duration of the study. Viral persistence in both CSF and LN correlated with upregulation of mechanistic target of rapamycin (mTOR), proinflammatory, and anti-apoptotic signaling pathways, as well as downregulation of extracellular matrix signaling pathways. These data raise the possibility that persistent or occult neurologic and lymphoid disease may occur following clearance of peripheral virus in ZIKV-infected individuals.
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Project description:Olfactory ensheathing cells are one of the few central nervous system regenerative cells discovered so far. It is characterized by its lifelong nerve regeneration function, and it can also release a variety of neurotrophic factors and neural adhesion molecules. It is considered to be the glial cell with the strongest myelination ability. Olfactory ensheathing cells and Schwann cells have phenotypes in common, they can promote axon regeneration(R. Doucette, 1995). Olfactory ensheathing cells have the characteristics of Schwann cells and astrocytes, but the overall performance tends to be the former, which has two unique characteristics. First, it exists not only in the peripheral nerves (Schwann cells), but also in the central nervous system (astroglia); second, the olfactory mucosa has the ability to regenerate life-long, including human olfactory ensheathing cells(J. C. Bartolomei and C. A. Greer, 2000). Regeneration is a process in which olfactory ensheathing cells participate in efficient regulation, although the specific mechanism is not yet clear. Olfactory ensheathing cells are different from astrocytes and Schwann cells, but at the same time have the characteristics of these two cells(S. C. Barnett, 2004), like Schwann cells help axon growth, but more than Schwann cells It can make axons grow long distances, that is, it has stronger migration(A. Ramon-Cueto et al., 1998); there are also astrocytes that have a nutritional effect on the survival of neurons and the growth of axons, but olfactory ensheathing cells can also wrap neurons forms myelin sheath to support the growth of nerve processes(R. Devon and R. Doucette, 1992; J. Gu et al., 2019). There are two characteristics that make olfactory ensheathing cells the best choice for the treatment of neurological diseases(S. C. Chiu et al., 2009; J. Kim et al., 2018; M. Abdel-Rahman et al., 2018). Olfactory ensheathing cells are gradually used to treat spinal cord injuries and have shown amazing effects(J. C. Bartolomei and C. A. Greer, 2000; K. J. Liu et al., 2010; R. Yao et al., 2018). Olfactory ensheathing cells that have been used in research are usually derived from the olfactory bulb(E. H. Franssen et al., 2007), but it is easier to obtain olfactory ensheathing cells from the olfactory mucosa in clinical practice(M. Ryszard et al., 2006), so the difference between the olfactory ensheathing cells from the olfactory bulb and the olfactory mucosa There are more and more studies(B. M. U. et al., 2007), and previous studies have shown that they not only have many similar functions, but also have many differences(M. W. Richter et al., 2005; L. Wang et al., 2014; K. E. Smith et al., 2020). Because olfactory ensheathing cells derived from the olfactory bulb are not easy to obtain, olfactory ensheathing cells derived from the olfactory mucosa have become the focus of attention. Although we know that olfactory ensheathing cells from two sources have nerve repair functions, it is not clear why the two different sources of olfactory ensheathing cells have different therapeutic effects. Nicolas G. once studied that the genetic difference between the two cells and found that there are many genes related to wound repair and nerve regeneration(G. Nicolas et al., 2010). We have reason to guess that olfactory ensheathing cells from these two sources will also have a large difference in protein level. Our research group wants to use the current mature transcriptome and proteomic sequencing technologies to explore the difference between olfactory ensheathing cells from the olfactory bulb and olfactory mucosa, and explain why the two sources of olfactory ensheathing cells shows different therapeutic effects, hope to provide a new theoretical basis for future clinical treatment.
2022-02-16 | PXD024046 | Pride