Non-permissive SARS-CoV-2 infection in human neurospheres

Pedrosa, Carolina da S. G.; Goto‐Silva, Livia; Temerozo, Jairo R.; Souza, Letícia R. Q.; Vitória, Gabriela; Ornelas, Isis M.; Karmirian, Karina; Mendes, Mayara Abud; Gomes, Ismael Carlos; Sacramento, Carolina Q.; Fintelman-Rodrigues, Natália; Soares, Vinícius Cardoso; Dias, Suelen da Silva Gomes; Salerno, José Alexandre; Puig‐Pijuan, Teresa; Oliveira, Jonice; Aragão, Luiz Guilherme H.S.; Torquato, Thayana; Veríssimo, Carla Pires; Biagi, Diogo; Cruvinel, Estela; Dariolli, Rafael; Furtado, Daniel Rodrigues; Borges, Helena L.; Bozza, Patrı́cia T.; Rehen, Stevens K.; Souza, Thiago Moreno L.; Guimarães, Marília Zaluar P.

doi:10.1016/j.scr.2021.102436

Cited by 18 publications

(11 citation statements)

References 103 publications

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“…SARS-CoV-2 has been detected in brain tissue, [ 106 , 115 , 116 ] including SARS-CoV-2 viral RNA transcripts [ 105 , 117 , 118 ], and viral proteins in the epithelial cells within the olfactory bulb [ 119 ]. However, on the other hand, studies showed that SARS-CoV-2 does not replicate in the CNS, and its CNS effects may be attributable to the immune responses that are triggered by the infection [ 120 , 121 ].…”

Section: Sars-cov-2 and The Nervous Systemmentioning

confidence: 99%

A Peek into Pandora’s Box: COVID-19 and Neurodegeneration

Chandra¹,

Johri²

2022

Brain Sciences

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Ever since it was first reported in Wuhan, China, the coronavirus-induced disease of 2019 (COVID-19) has become an enigma of sorts with ever expanding reports of direct and indirect effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on almost all the vital organ systems. Along with inciting acute pulmonary complications, the virus attacks the cardiac, renal, hepatic, and gastrointestinal systems as well as the central nervous system (CNS). The person-to-person variability in susceptibility of individuals to disease severity still remains a puzzle, although the comorbidities and the age/gender of a person are believed to play a key role. SARS-CoV-2 needs angiotensin-converting enzyme 2 (ACE2) receptor for its infectivity, and the association between SARS-CoV-2 and ACE2 leads to a decline in ACE2 activity and its neuroprotective effects. Acute respiratory distress may also induce hypoxia, leading to increased oxidative stress and neurodegeneration. Infection of the neurons along with peripheral leukocytes’ activation results in proinflammatory cytokine release, rendering the brain more susceptible to neurodegenerative changes. Due to the advancement in molecular biology techniques and vaccine development programs, the world now has hope to relatively quickly study and combat the deadly virus. On the other side, however, the virus seems to be still evolving with new variants being discovered periodically. In keeping up with the pace of this virus, there has been an avalanche of studies. This review provides an update on the recent progress in adjudicating the CNS-related mechanisms of SARS-CoV-2 infection and its potential to incite or accelerate neurodegeneration in surviving patients. Current as well as emerging therapeutic opportunities and biomarker development are highlighted.

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Section: Sars-cov-2 and The Nervous Systemmentioning

confidence: 99%

A Peek into Pandora’s Box: COVID-19 and Neurodegeneration

Chandra¹,

Johri²

2022

Brain Sciences

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“…Tissue samples showed a high viral load at seven days post-inoculation despite the absence of productive infection, as determined by analyzing supernatant samples. Similarly, non-productive (abortive) SARS-CoV-2 infections have been described in neural tissue [24,27]. Here, the presented data only provide initial insights and require further dissection of viral attachment or entry mechanisms.…”

Section: Discussionmentioning

confidence: 84%

RT-PCR Testing of Organ Culture Medium for Corneal Storage Fails to Detect SARS-CoV-2 Infection Due to Lack of Viral Replication

et al. 2022

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Concerns of possible transmission of SARS-CoV-2 from donors to patients by corneal transplantation have caused a decline in corneal transplantations. Graft culture media are routinely tested for infectious risks, but it is unclear whether this constitutes a viable means to avoid transmitting SARS-CoV-2 via keratoplasty. We found that SARS-CoV-2 RNA was not present in the medium after seven days of organ culture of corneas from donors (n = 4), who were SARS-CoV-2-positive upon tissue procurement. These medium samples showed no presence of viral RNA. To pursue this question under controlled conditions and further exclude the possibility of productive infection in corneal grafts, we inoculated corneoscleral discs from healthy donors (n = 8) with infectious SARS-CoV-2 and performed PCR testing of the culture medium at various time points. After seven days of culture, we also tested for SARS-CoV-2 RNA within the inoculated corneal tissue. The medium from tissue samples inoculated with SARS-CoV-2 showed no increase in viral RNA, which may indicate lack of viral replication in these corneal grafts. SARS-CoV-2-RNA was, however, detected on or in corneal tissue seven days after inoculation. Our data suggest that corneal grafts may not be permissive for replication of SARS-CoV-2 and demonstrates that PCR testing of culture media cannot safely exclude that tissue has been exposed to SARS-CoV-2. It also demonstrates the difficulty to differentiate between virus adherence and virus replication by PCR testing in SARS-CoV-2 exposed tissue.

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“…Despite the numerous reports on COVID-19, it is still debatable if SARS-CoV-2 invades the Central Nervous System (CNS) via olfactory neurons (27) and infects neurons and glia of the CNS (28)(29)(30)(31)(32)(33)(34)(35). Different groups have shown that human neural progenitor cells, grown either as brain organoids or as neurospheres, are permissive to SARS-CoV-2 infection (30,(35)(36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 Permissive Glioblastoma Cell Line for High Throughput Antiviral Screening

Vanhulle

Stroobants

Provinciael

et al. 2022

Preprint

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Despite the great success of the administered vaccines against SARS-CoV-2, the virus can still spread, as evidenced by the current circulation of the highly contagious Omicron variant. This emphasizes the additional need to develop effective antiviral countermeasures. In the context of early preclinical studies for antiviral assessment, robust cellular infection systems are required to screen drug libraries. In this study, we reported the implementation of a human glioblastoma cell line, stably expressing ACE2, in a SARS-CoV-2 cytopathic effect (CPE) reduction assay. These glioblastoma cells, designated as U87.ACE2+, expressed ACE2 and cathepsin B abundantly, but had low cellular levels of TMPRSS2 and cathepsin L. The U87.ACE2+ cells fused highly efficiently and quickly with SARS-CoV-2 spike expressing cells. Furthermore, upon infection with SARS-CoV-2 wild-type virus, the U87.ACE2+ cells displayed rapidly a clear CPE that resulted in complete cell lysis and destruction of the cell monolayer. By means of several readouts we showed that the U87.ACE2+ cells actively replicate SARS-CoV-2. Interestingly, the U87.ACE2+ cells could be successfully implemented in an MTS-based colorimetric CPE reduction assay, providing IC50 values for Remdesivir in the low nanomolar range. Lastly, the U87.ACE2+ cells were consistently permissive to all tested SARS-CoV-2 variants of concern, including the current Omicron variant. Thus, ACE2 expressing glioblastoma cells are highly permissive to SARS-CoV-2 with productive viral replication and with the induction of a strong CPE that can be utilized in high-throughput screening platforms.

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Non-permissive SARS-CoV-2 infection in human neurospheres

Abstract: Graphical abstract

Cited by 18 publications

References 103 publications

A Peek into Pandora’s Box: COVID-19 and Neurodegeneration

A Peek into Pandora’s Box: COVID-19 and Neurodegeneration

RT-PCR Testing of Organ Culture Medium for Corneal Storage Fails to Detect SARS-CoV-2 Infection Due to Lack of Viral Replication

SARS-CoV-2 Permissive Glioblastoma Cell Line for High Throughput Antiviral Screening

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